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1.
Drug Dev Res ; 85(1): e22142, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38349266

RESUMO

Thyroid cancer is a highly differentiated and poorly malignant tumor. Interfering with glycolysis has become an effective means of controlling cancer progression and autophagy is negatively correlated with glycolysis. Aldo-keto reductase family 1 member C3 (AKR1C3) has been demonstrated to be highly expressed in thyroid cancer tissue and the higher AKR1C3 expression predicted the worse prognosis. We aimed to explore whether AKR1C3 could affect thyroid cancer progression by regulating autophagy-dependent glycolysis. AKR1C3 expression in thyroid cancer cells was detected by western blot. Then, AKR1C3 was knocked down by transfection with short hairpin RNA specific to AKR1C3 in the absence or presence of 3-methyladenine (3-MA) or PMA treatment. Cell cycle and apoptosis was detected by flow cytometry. Immunofluorescence staining was used to analyze LC3B expression. Extracellular acidification, glucose uptake and lactic acid secretion were detected. To evaluate the tumorigenicity of AKR1C3 insufficiency on thyroid cancer in vivo, TPC-1 cells with AKR1C3 knockdown were injected subcutaneously into nude mice. Then, cyclinD1 and Ki67 expression in tumorous tissues was measured by immunohistochemical analysis. Apoptosis was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling staining. Additionally, the expression of proteins related to cell cycle, apoptosis, glycolysis, autophagy, and extracellular signal-regulated kinase (ERK) signaling in cells and tumor tissues was assessed by western blot. Highly expressed AKR1C3 was observed in thyroid cancer cells. AKR1C3 knockdown induced cell cycle arrest and apoptosis of TPC-1 cells. Besides, autophagy was activated and glycolysis was inhibited following AKR1C3 silencing, and 3-MA treatment restored the impacts of AKR1C3 silencing on glycolysis. The further experiments revealed that AKR1C3 insufficiency inhibited ERK signaling and PMA application reversed AKR1C3 silencing-induced autophagy in TPC-1 cells. The in vivo results suggested that AKR1C3 knockdown inhibited the development of subcutaneous TPC-1 tumors in nude mice and inactivated the ERK signaling. Collectively, AKR1C3 silencing inhibited autophagy-dependent glycolysis in thyroid cancer by inactivating ERK signaling.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular , Neoplasias da Glândula Tireoide , Animais , Camundongos , Membro C3 da Família 1 de alfa-Ceto Redutase , Autofagia , Glicólise , Camundongos Nus , Neoplasias da Glândula Tireoide/genética , Humanos
2.
Immun Inflamm Dis ; 12(1): e1150, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38270308

RESUMO

BACKGROUND: Recently, many studies have been conducted to examine immune response modification at epigenetic level, but the candidate effect of RNA 5-methylcytosine (m5 C) modification on tumor microenvironment (TME) of acute myeloid leukemia (AML) is still unknown at present. METHODS: We assessed the patterns of m5 C modification among 417 AML cases by using nine m5 C regulators. Thereafter, we associated those identified modification patterns with TME cell infiltration features. Additionally, stepwise regression and LASSO Cox regression analyses were conducted for quantifying patterns of m5 C modification among AML cases to establish the m5 C-score. Meanwhile, we validated the expression of genes in the m5C-score model by qRT-PCR. Finally, the present work analyzed the association between m5 C-score and AML clinical characteristics and prognostic outcomes. RESULTS: In total, three different patterns of m5 C modification (m5 C-clusters) were identified, and highly differentiated TME cell infiltration features were also identified. On this basis, evaluating patterns of m5 C modification in single cancer samples was important for evaluating the immune/stromal activities in TME and for predicting prognosis. In addition, the m5 C-score was established, which showed a close relation with the overall survival (OS) of test and training set samples. Moreover, multivariate Cox analysis suggested that our constructed m5 C-score served as the independent predicting factor for the prognosis of AML (hazard ratio = 1.57, 95% confidence interval = 1.38-1.79, p < 1e-5 ). CONCLUSIONS: This study shows that m5 C modification may be one of the key roles in the formation of diversity and complexity of TME. Meanwhile, assessing the patterns of m5 C modification among individual cancer samples is of great importance, which provides insights into cell infiltration features within TME, thereby helping to develop relevant immunotherapy and predict patient prognostic outcomes.


Assuntos
Leucemia Mieloide Aguda , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Leucemia Mieloide Aguda/genética , RNA , Diferenciação Celular , Metilação
3.
Dalton Trans ; 52(48): 18247-18256, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37997638

RESUMO

The direct oxygenation of alkylarenes at the benzylic position employing bioinspired nonheme catalysts has emerged as a promising strategy for the production of bioactive arene ketone scaffolds in drugs. However, the structure-activity relationship of the active species and the mechanism of these reactions remain elusive. Herein, the reaction mechanism of the Mn(II)-mediated benzylic oxygenation of phenylbutanoic acid (PBA) to 4-oxo-4-phenylbutyric acid (4-oxo-PBA) by H2O2 was investigated using density functional theory calculations. The calculated results demonstrated that the MnIII-OOH species (1) is a sluggish oxidant and needs to be converted to a high-valent manganese-oxo species (2). The conversion of PBA to 4-oxo-PBA by 2 occurs via the consecutive hydroxylation of PBA to 4-hydroxyl-4-phenylbutyric acid (4-OH-PBA) and the alcohol oxidation of 4-OH-PBA to 4-oxo-PBA. The hydroxylation of PBA proceeds via a novel hydride transfer/hydroxyl-rebound mechanism and the alcohol oxidation of 4-OH-PBA occurs via three pathways (gem-diol, dual hydrogen abstraction (DHA), and reversed-DHA pathways). The regio-selectivity of benzylic oxidations was caused by a strong π-π stacking interaction between the pyridine ring of the nonheme ligand and the phenyl ring of the substrate. These mechanistic findings enrich the knowledge of biomimetic alcohol oxidations and play a positive role in the rational design of new non-heme catalysts.

4.
Transl Oncol ; 36: 101747, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37517143

RESUMO

Head and neck squamous cell carcinomas (HNSCC) are at a high risk of recurrence and multimodal therapy have not significantly improved survival in recent decades. Although immune checkpoint inhibitors (ICIs) are effective in a small proportion of HNSCC patients, the majority do not respond. In this study, we for the first time revealed that xenobiotic metabolic process was significantly associated with resistance to programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in HNSCC and found that ATP binding cassette subfamily B member 11 (ABCB11) accumulated in immature tertiary lymphoid structures (TLSs) predicted worse progression-free survival (PFS) and overall survival (OS) after PD-1/PD-L1 inhibitors therapy. Moreover, the expression of cytochrome P450 1A2 (CYP1A2), a cytochrome P450 (CYP) enzyme that participates in xenobiotic metabolic process, was significantly upregulated in CD45+ABCB11+ tumor-infiltrating lymphocytes (TILs) compared with CD45+ABCB11-TILs in HNSCC tissues. Whole slide scans of 110 HNSCC tissues with hematoxylin-eosin (HE) and multispectral immuno-fluorescent (mIF) staining revealed that ABCB11 had a high co-expression with CYP1A2 in immature TLSs, and colocalization of ABCB11 and CYP1A2 in immature TLs significantly associated with high infiltration of immunosuppressive T-regulatory (Treg). Our study revealed that ABCB11 accumulated in immature TLSs might upregulate CYP1A2 to mediate xenobiotic metabolic process, thus increase the immunosuppressive Treg infiltration, and induce resistance to PD-1/PD-L1 inhibitors in HNSCC.

5.
Chem Commun (Camb) ; 59(39): 5890-5893, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37097118

RESUMO

Herein we report two 2D layered metal-organic rotaxane frameworks (MORFs), WUST-1 and WUST-2, constituted by a ternary host-guest complex based on cucurbit[8]uril (CB[8]) and an (E)-1-methyl-4-[4-(pyridin-4-yl)styryl] pyridinium (G1) ligand, and different metal ions and auxiliary linkers. Both MORFs are stable in water and highly fluorescence emissive, and can selectively sense nitrofurazone with low detection limits.

6.
Front Endocrinol (Lausanne) ; 14: 1102777, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36864842

RESUMO

Objective: Familial dysalbuminemic hyperthyroxinemia (FDH) has not been thoroughly studied in the Chinese population to date. The clinical characteristics of FDH in Chinese patients were summarized, and the susceptibility of common free thyroxine (FT4) immunoassay methods was evaluated. Methods: The study included 16 affected patients from eight families with FDH admitted to the First Affiliated Hospital of Zhengzhou University. The published FDH patients of Chinese ethnicity were summarized. Clinical characteristics, genetic information, and thyroid function tests were analyzed. The ratio of FT4 to the upper limit of normal (FT4/ULN) in three test platforms was also compared in patients with R218H ALB mutation from our center. Results: The R218H ALB mutation was identified in seven families and the R218S in one family. The mean age of diagnosis was 38.4 ± 19.5 years. Half of the probands (4/8) were misdiagnosed as hyperthyroidism previously. The ratios of serum iodothyronine concentration to ULN in FDH patients with R218S were 8.05-9.74 for TT4, 0.68-1.28 for TT3, and 1.20-1.39 for rT3, respectively. The ratios in patients with R218H were 1.44 ± 0.15, 0.65 ± 0.14, and 0.77 ± 0.18, respectively. The FT4/ULN ratio detected using the Abbott I4000 SR platform was significantly lower than Roche Cobas e801 and Beckman UniCel Dxl 800 Access platforms (P < 0.05) in patients with R218H. In addition, nine Chinese families with FDH were retrieved from the literature, of which eight carried the R218H ALB mutation and one the R218S. The TT4/ULN of approximately 90% of patients (19/21) with R218H was 1.53 ± 0.31; the TT3/ULN of 52.4% of patients (11/21) was 1.49 ± 0.91. In the family with R218S, 45.5% of patients (5/11) underwent TT4 dilution test and the TT4/ULN was 11.70 ± 1.33 and 90.9% (10/11) received TT3 testing and the TT3/ULN was 0.39 ± 0.11. Conclusions: Two ALB mutations, R218S and R218H, were found in eight Chinese families with FDH in this study, and the latter may be a high-frequency mutation in this population. The serum iodothyronine concentration varies with different mutation forms. The rank order of deviation in measured versus reference FT4 values by different immunoassays (lowest to highest) was Abbott < Roche < Beckman in the FDH patients with R218H.


Assuntos
Hipertireoxinemia Disalbuminêmica Familiar , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Hipertireoxinemia Disalbuminêmica Familiar/diagnóstico , Hipertireoxinemia Disalbuminêmica Familiar/genética , Tiroxina , População do Leste Asiático , Hormônios Tireóideos , Imunoensaio
7.
Open Med (Wars) ; 18(1): 20230660, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36880066

RESUMO

This study aimed to explore the prognostic and predictive value of autophagy-related lncRNAs in papillary thyroid carcinoma (PTC). The expression data of autophagy-related genes and lncRNAs of the PTC patients were obtained from TCGA database. Autophagy-related-differentially expressed lncRNAs (DElncs) were identified and used to establish the lncRNAs signature predicting patients' progression-free interval (PFI) in the training cohort. Its performance was assessed in the training cohort, validation cohort, and entire cohort. Effects of the signature on I-131 therapy were also explored. We identified 199 autophagy-related-DElncs and constructed a novel six-lncRNAs signature was constructed based on these lncRNAs. This signature had a good predictive performance and was superior to TNM stages and previous clinical risk scores. I-131 therapy was found to be associated with favorable prognosis in patients with high-risk scores but not those with low-risk scores. Gene set enrichment analysis suggested that a series of hallmark gene sets were enriched in the high-risk subgroup. Single-cell RNA sequencing analysis suggested that the lncRNAs were mainly expressed in thyroid cells but not stromal cells. In conclusion, our study constructed a well-performed six-lncRNAs signature to predict PFI and I-131 therapy benefits in PTC.

8.
Phys Rev Lett ; 129(23): 235001, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36563203

RESUMO

Solids ablate under laser irradiation, but experiments have not previously characterized the initiation of this process at ultrarelativistic laser intensities. We present first measurements of bulk ion velocity distributions as ablation begins, captured as a function of depth via Doppler-shifted x-ray line emission from two viewing angles. Bayesian analysis indicates that bulk ions are either nearly stationary or flowing outward at the plasma sound speed. The measurements quantitatively constrain the laser-plasma ablation mechanism, suggesting that a steplike electrostatic potential structure drives solid disassembly.

9.
Rev Sci Instrum ; 93(10): 103527, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319349

RESUMO

A high-resolution x-ray spectrometer was coupled with an ultrafast x-ray streak camera to produce time-resolved line shape spectra measured from hot, solid-density plasmas. A Bragg crystal was placed near laser-produced plasma to maximize throughput; alignment tolerances were established by ray tracing. The streak camera produced single-shot, time-resolved spectra, heavily sloped due to photon time-of-flight differences, with sufficient reproducibility to accumulate photon statistics. The images are time-calibrated by the slope of streaked spectra and dewarped to generate spectra emitted at different times defined at the source. The streaked spectra demonstrate the evolution of spectral shoulders and other features on ps timescales, showing the feasibility of plasma parameter measurements on the rapid timescales necessary to study high-energy-density plasmas.

10.
Front Endocrinol (Lausanne) ; 13: 800135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295993

RESUMO

Objective: A Rathke's cleft cyst (RCC) is a common, benign, cystic disease that often leads to hypophyseal dysfunction or head symptoms. The relationship between RCCs and pituitary gland function is not clear. We therefore carried out a study to examine this relationship in greater detail. Methods: The study was a retrospective, cohort design in patients diagnosed with a RCC between January 2019 to July 2021 at the First Affiliated Hospital of Zhengzhou University, China. Results: A total of 221 patients were enrolled and then divided into study cohorts according to the diameter of the RCC, clinical manifestations, and surgical treatment received. The majority of patients were symptomatic (143/221), including 83 cases of dizziness and headache, 9 of vision loss and visual field defect, and 2 of diabetes insipidus. 52 cases had abnormal pituitary function, with 8 cases interestingly showing high adrenocorticotropic-hormone (ACTH) and cortisone levels, while 8 juvenile cases had developed central precocious puberty. Patients with larger RCCs were more likely to present with headaches and dizziness, with subjects who suffered from these symptoms having high ACTH and cortisone levels. Conclusion: Although the size of a RCC is not an important factor influencing hypopituitary function, we consider that endocrine evaluation should be carried out in all patients with a RCC.


Assuntos
Carcinoma de Células Renais , Cistos do Sistema Nervoso Central , Cortisona , Neoplasias Renais , Doenças da Hipófise , Neoplasias Hipofisárias , Hormônio Adrenocorticotrópico , Cistos do Sistema Nervoso Central/complicações , Tontura , Feminino , Humanos , Masculino , Doenças da Hipófise/complicações , Doenças da Hipófise/epidemiologia , Hipófise , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos
11.
ISA Trans ; 129(Pt B): 673-683, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35279310

RESUMO

As a data-driven design method, model-free optimal control based on reinforcement learning provides an effective way to find optimal control strategies. The design of model-free optimal control is sensitive to system data because it relies on data rather than detailed dynamic models. A prerequisite for generating applicable data is that the system must be open-loop stable (with a stable equilibrium point), which restricts the data-based control design methods in actual control problems and leads to rare experimental studies or verification in the literature. To improve this situation and enrich its applications, we propose a pre-stabilized mechanism and apply it to the motion control of a mechanical system together with a reinforcement learning-based model-free optimal control method, which constitutes a so-called hierarchical control structure. We design two real-time control experiments on an underactuated system to verify its effectiveness. The control results show that the proposed hierarchical control is quite promising in controlling this mechanical system, even though it is open-loop unstable with unknown dynamics.

12.
Hepatology ; 75(5): 1218-1234, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34591986

RESUMO

BACKGROUND AND AIMS: NAFLD is considered as the hepatic manifestation of the metabolic syndrome, which includes insulin resistance, obesity and hyperlipidemia. NASH is a progressive stage of NAFLD with severe hepatic steatosis, hepatocyte death, inflammation, and fibrosis. Currently, no pharmacological interventions specifically tailored for NASH are approved. Ovarian tumor domain, ubiquitin aldehyde binding 1 (OTUB1), the founding member of deubiquitinases, regulates many metabolism-associated signaling pathways. However, the role of OTUB1 in NASH is unclarified. METHODS AND RESULTS: We demonstrated that mice with Otub1 deficiency exhibited aggravated high-fat diet-induced and high-fat high-cholesterol (HFHC) diet-induced hyperinsulinemia and liver steatosis. Notably, hepatocyte-specific overexpression of Otub1 markedly alleviated HFHC diet-induced hepatic steatosis, inflammatory responses, and liver fibrosis. Mechanistically, we identified apoptosis signal-regulating kinase 1 (ASK1) as a key candidate target of OTUB1 through RNA-sequencing analysis and immunoblot analysis. Through immunoprecipitation-mass spectrometry analysis, we further found that OTUB1 directly bound to tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppressed its lysine 63-linked polyubiquitination, thus inhibiting the activation of ASK1 and its downstream pathway. CONCLUSIONS: OTUB1 is a key suppressor of NASH that inhibits polyubiquitinations of TRAF6 and attenuated TRAF6-mediated ASK1 activation. Targeting the OTUB1-TRAF6-ASK1 axis may be a promising therapeutic strategy for NASH.


Assuntos
Cisteína Endopeptidases/metabolismo , Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Transdução de Sinais , Fator 6 Associado a Receptor de TNF
13.
Phys Rev Lett ; 127(20): 205001, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34860067

RESUMO

Heß spectral line shapes are important for diagnosing temperature and density in many dense plasmas. This work presents Heß line shapes measured with high spectral resolution from solid-density plasmas with minimized gradients. The line shapes show hallmark features of Stark broadening, including quantifiable redshifts and double-peaked structure with a significant dip between the peaks; these features are compared to models through a Markov chain Monte Carlo framework. Line shape theory using the dipole approximation can fit the width and peak separation of measured line shapes, but it cannot resolve an ambiguity between electron density n_{e} and ion temperature T_{i}, since both parameters influence the strength of quasistatic ion microfields. Here a line shape model employing a full Coulomb interaction for the electron broadening computes self-consistent line widths and redshifts through the monopole term; redshifts have different dependence on plasma parameters and thus resolve the n_{e}-T_{i} ambiguity. The measured line shapes indicate densities that are 80-100% of solid, identifying a regime of highly ionized but well-tamped plasma. This analysis also provides the first strong evidence that dense ions and electrons are not in thermal equilibrium, despite equilibration times much shorter than the duration of x-ray emission; cooler ions may arise from nonclassical thermalization rates or anomalous energy transport. The experimental platform and diagnostic technique constitute a promising new approach for studying ion-electron equilibration in dense plasmas.

14.
Front Cell Dev Biol ; 9: 752990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869341

RESUMO

Osteoporosis (OP) is a chronic disease in the elderly, and China is entering an aging demographic trend. In recent years, increasing evidence has demonstrated that probiotics can treat osteoporosis. This study aimed to explore the relevant mechanisms and to validate the beneficial effect on osteoporosis by high-throughput metagenome-wide gene sequencing in humans. In this study, compared with controls, several species had altered abundances, and specific functional pathways were found in the OP group. At the species level, the species that had increased in OP individuals were positively correlated to bone resorption markers and negatively correlated to 25-OH-D3 and bone formation markers, with Streptococcus sanguinis showing the strongest relevance, followed by Streptococcus gordonii, Actinomyces odontolyticus, and Olsenella unclassified. Additionally, Actinomyces graevenitzii, enriched in the OP group, was positively correlated to inflammation indicators that included white blood cell (WBC), neutrophil count (NEC), and the neutrophil-to-lymphocyte ratio (NLR) (p < 0.05). Conversely, the levels of Akkermansia muciniphila, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides uniformis, and Butyricimonas synergistic were increased in the control group, which had a negative correlation with bone resorption markers and positive correlation with bone formation markers and 25-OH-D3. Additionally, Bacteroides fragilis had a negative correlation with inflammation indicators (WBC, NEC, and NLR) and the above pathways (p < 0.05). Functional prediction revealed that 106 metabolic pathways, enriched in the OP group, were significantly higher than in the control group (p < 0.05). In particular, pathways related to LPS biosynthesis, phytate degradation, lactate acid, and ethanol fermentation were more abundant in the OP group than in the control and were positively related to WBC and NEC. Taken together, several species with altered abundances and specific functional pathways were found in OP individuals. The role of phytases in OP provides novel epidemiological evidence to elucidate the underlying microbiota-relevant mechanisms in bone mineralization and should be explored further.

15.
Comput Methods Programs Biomed ; 212: 106467, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34715519

RESUMO

BACKGROUND AND OBJECTIVE: Computed tomography (CT) examination plays an important role in screening suspected and confirmed patients in pneumocystis carinii pneumonia (PCP), and the efficient acquisition of high-quality medical CT images is essential for the clinical application of computer-aided diagnosis technology. Therefore, improving the resolution of CT images of pneumonia is a very important task. METHODS: Aiming at the problem of how to recover the texture details of the reconstructed PCP CT super-resolution image, we propose the image super-resolution reconstruction model based on self-attention generation adversarial network (SAGAN). In the SAGAN algorithm, a generator based on self-attention mechanism and residual module is used to transform a low-resolution image into a super-resolution image. A discriminator based on depth convolution network tries to distinguish the difference between the reconstructed super-resolution image and the real super-resolution image. In terms of loss function construction, on the one hand, the Charbonnier content loss function is used to improve the accuracy of image reconstruction, and on the other hand, the feature value before activation of the pre-trained VGGNet is used to calculate the perceptual loss to achieve accurate texture detail reconstruction of super-resolution images. RESULTS: Experimental results show that our SAGAN algorithm is superior to other state-of-the-art algorithms in both peak signal-to-noise ratio (PSNR) and structural similarity score (SSIM). Specifically, our SAGAN method can obtain 31.94 dB which is 1.53 dB better than SRGAN on Set5 dataset for 4 enlargements. CONCLUSION: Our SAGAN method can reconstruct more realistic PCP CT images with clear texture, which can help experts diagnose the condition of PCP.


Assuntos
Pneumonia por Pneumocystis , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador , Pneumonia por Pneumocystis/diagnóstico por imagem , Razão Sinal-Ruído , Tomografia Computadorizada por Raios X
16.
Materials (Basel) ; 14(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34501198

RESUMO

The properties of the MoS2/Zr coatings can be significantly affected by the deposition temperature. In this study, the MoS2/Zr composite coatings were fabricated on the cemented carbide surface, utilizing the duplex deposition technology at various deposition temperatures. The effects of deposition temperature on the mechanical and friction properties of the MoS2/Zr coatings were systematically studied. Results exhibited that as the deposition temperature increased, the adhesion force increased first and then decreased, and the coating thickness and micro-hardness gradually increased. Dry sliding tests against a hardened steel ring showed that the tribological behaviors and wear mechanisms of the MoS2/Zr coatings varied with deposition temperature, which were due to the changing mechanical properties of coatings caused by the temperature. The coatings deposited at a temperature of 180 °C and 200 °C possessed preferable comprehensive mechanical and tribological properties.

17.
Eur J Pharmacol ; 911: 174482, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34481875

RESUMO

Berberine facilitates the production of glucagon-like peptide-1 (GLP-1) by intestinal L cells. Here, we aimed to reveal the mechanism of berberine facilitating the production of GLP-1 by intestinal L cells. In this study, we confirmed that the 100 mg/kg berberine daily through diet decreased the miR-106b expression and elevated the expressions of ß-catenin and T-cell factor 4 (TCF4) in colon tissues of high-fat diet mice; berberine decreased the concentrations of triglycerides, total cholesterol and the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in mouse serum samples; berberine decreased the blood glucose in the mouse tail vein blood and promoted GLP-1 production by intestinal L cells in mouse serum samples and elevated the GLP-1 expression in mouse colon tissues. Meanwhile, the mechanism analysis demonstrated that a dose of 100 µM berberine down-regulated the miR-106b expression by elevating the methylation levels of miR-106b in STC-1 cells and miR-106b bound to TCF4 in 293T cells. Moreover, the 100 mg/kg berberine daily through diet activated the ß-catenin/TCF4 signaling pathway by decreasing miR-106b, thereby facilitating GLP-1 production in intestinal L cells through the in vivo assays. Conclusively, our experimental data illustrated that berberine decreased miR-106b expression by increasing its methylation levels and then activated the ß-catenin/TCF4 signaling pathway, thereby facilitating GLP-1 production by intestinal L cells.


Assuntos
beta Catenina
18.
Front Microbiol ; 12: 682721, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335505

RESUMO

Metabolic syndrome (MetS) is a wide-ranging disorder, which includes insulin resistance, altered glucose and lipid metabolism, and increased blood pressure and visceral obesity. MetS symptoms combine to result in a significant increase in cardiovascular risk. It is therefore critical to treat MetS in the early stages of the disorder. In this study, 123 MetS patients and 304 controls were recruited to determine whether the gut microbiome plays a role in MetS development and progression. By using whole-genome shotgun sequencing, we found that the gut microbiomes of MetS patients were different from those of controls, with MetS patients possessing significantly lower gut microbiome diversity. In addition, 28 bacterial species were negatively correlated with waist circumstance, with Alistipes onderdonkii showing the strongest correlation, followed by Bacteroides thetaiotaomicron, Clostridium asparagiforme, Clostridium citroniae, Clostridium scindens, and Roseburia intestinalis. These species were also enriched in controls relative to MetS patients. In addition, pathways involved in the biosynthesis of carbohydrates, fatty acids, and lipids were enriched in the MetS group, indicating that microbial functions related to fermentation may play a role in MetS. We also found that microbiome changes in MetS patients may aggravate inflammation and contribute to MetS diseases by inhibiting the production of short-chain fatty acids (SCFAs). Taken together, these results indicate the potential utility of beneficial gut microbiota as a potential therapeutic to alleviate MetS.

19.
Sci Rep ; 11(1): 11076, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34040142

RESUMO

Obesity, especially abdominal obesity, is correlated to increased risk of cardiovascular morbidity and mortality. It is urgent to search a simply method to predict visceral fat area (VFA). Herein, we evaluated the correlation of waist circumference (WC) measured by anthropometry and bioelectrical impedance analysis (BIA), and VFA estimated by BIA or measured by quantitative computed tomography (QCT) in China. The mean body mass index (BMI) was 25.09 ± 3.31 kg/m2 and the mean age was 49.16 ± 9.19 years in 2754 subjects. VFA-BIA were significantly smaller than VFA-QCT in both BMI and age subgroups between male and female (p < 0.001). High correlation was observed for WC between BIA and manually (r = 0.874 for all, r = 0.865 for male and r = 0.806 for female) and for VFA between BIA and QCT (r = 0.512 for all). The intraclass correlation coefficient (ICC) showed the perfect agreement between BIA and manually to measure WC (ICC = 0.832 for all, 0.845 for male and 0.697 for female) and implied a good reliability for VFA between BIA and QCT with women among subgroups (ICC = 0.623 for all, ICC = 0.634 for age < 50 years and ICC = 0.432 for BMI > 24 kg/m2), whereas the good reliability was lost in men (ICC = 0.174). The kappa analysis showed a moderate consistency for VFA measured by BIA and QCT (Kappa = 0.522 with age < 50 years, 0.565 with age ≥ 50 years in male; Kappa = 0.472 with age < 50 years, 0.486 with age ≥ 50 years in female). In addition, BIA to estimate VFA (r = 0.758 in male, r = 0.727 in female, P < 0.001) has a stronger correlation with VFA measured by QCT than BMI and WC according to gender categories. Furthermore, ROC analysis showed the cut-off point of VFA measured by BIA for predicting visceral obesity was: 101.90 cm2, 119.96 cm2 and 118.83 cm2 and the Youden's index was 0.577, 0.577 and 0.651, respectively and the Kappa value was 0.532, 0.536 and 0.611 in unadjusted model, model 1 and model 2. In conclusion, being non-invasive and free of radiation, BIA can be used as a safe and convenient tool to estimate VFA in female; especially for monitoring the VFA of the same person, the BIA has superiority to a certain extent. However, the consistency is not most ideal between BIA and QCT. When using BIA to assess whether a person is visceral obesity, we must take into consideration age, BMI and WC. Therefore, we established a regression formula to reflect VFA-QCT by VFA-BIA, age, BMI, and WC. In addition, a more accurate formula is needed to match the CT data in China.


Assuntos
Antropometria/métodos , Composição Corporal/fisiologia , Impedância Elétrica , Tomografia Computadorizada por Raios X/métodos , Circunferência da Cintura/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Rev Sci Instrum ; 92(3): 033525, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33820090

RESUMO

Fine-structure x-ray spectra have been measured from foils with embedded tracer layers at two laser facilities. A suite of layered foils with thin Ti tracers under varied tamper layers was studied at both the Titan and the ALEPH 400 nm laser facilities, where Ti Heα emission was recorded using a high-resolution Bragg crystal spectrometer. Several indicators of plasma parameters are examined in the spectra, including temperature- and density-dependent line ratios and line broadening from Stark and opacity effects. Spectra indicate that (1) the plasma density at ALEPH is significantly higher than at Titan and (2) the electron temperature is high for near-surface layers at both facilities but drops more quickly with depth at ALEPH. These inferences of plasma conditions are consistent with differing levels of temporal contrast at each laser facility.

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