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1.
Nat Mater ; 23(4): 527-534, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38454027

RESUMO

The liquid-like feature of thermoelectric superionic conductors is a double-edged sword: the long-range migration of ions hinders the phonon transport, but their directional segregation greatly impairs the service stability. We report the synergetic enhancement in figure of merit (ZT) and stability in Cu1.99Se-based superionic conductors enabled by ion confinement effects. Guided by density functional theory and nudged elastic band simulations, we elevated the activation energy to restrict ion migrations through a cation-anion co-doping strategy. We reduced the carrier concentration without sacrificing the low thermal conductivity, obtaining a ZT of ∼3.0 at 1,050 K. Notably, the fabricated device module maintained a high conversion efficiency of up to ∼13.4% for a temperature difference of 518 K without obvious degradation after 120 cycles. Our work could be generalized to develop electrically and thermally robust functional materials with ionic migration characteristics.

2.
Opt Express ; 32(8): 14102-14115, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859365

RESUMO

A novel parallel beam combined lens (PBCL) was designed based on a parabolic monocapillary x-ray lens (PMXRL). The proposed PBCL converted a divergent X-ray beam into a near-solid parallel one, which retains the low divergence characteristics of PMXRL and significantly improves the intensity gain by about one order of magnitude. Compared with the traditional polycapillary parallel x-ray lens (PPXRL), the divergence performance of this lens is improved by an order of magnitude, and the light intensity gain is improved by 3-4 times. In addition, we developed a MATLAB-based visualization tool to simulate X-ray transmission within the PBCL through ray tracing. This tool facilitated the assessment of the PBCL's transmission efficiency and its comparison with conventional PMXRL and the PPXRL. The transport process of the PBCL is systematically investigated under the comprehensive consideration of multiple parameters. This study provided a new idea and theoretical basis for the further development of X-ray modulation technology.

3.
Opt Lett ; 49(2): 274-277, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38194546

RESUMO

X ray ghost imaging (XGI) offers both radiation dose-reduction potential and cost-effective benefits owing to the utilization of a single-pixel detector. Most XGI schemes with laboratory x ray sources require a mechanically moving mask for either structured illumination or structured detection. In either configuration, however, its resolution remains limited by the source size and the unit size of the mask. Upon propagation, the details of the object can actually be magnified by the divergence of x rays, but at the same time, the penumbra effect produced by the finite source size is dramatically intensified, which ultimately leads to a degradation of image quality in XGI. To address these limitations, this work proposes a magnified XGI scheme using structured detection equipped with tapered polycapillary optics, which can efficiently suppress the object's penumbra as well as resolve the magnified details of the object. In general, the resolution of this scheme is no longer affected by the source size but by the microcapillary size of polycapillary. Our work fundamentally achieves cancellation of penumbra effect-induced aberration, thus paving the way for high-resolution magnified XGI.

4.
Nurs Health Sci ; 26(2): e13129, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38781983

RESUMO

Adherence to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) post-stroke is often problematic, despite potential benefits. This study aimed to evaluate CPAP adherence in patients with OSA post-stroke based on the Andersen behavioral model of health services utilization. A total of 227 eligible participants were recruited from a Chinese hospital. After baseline assessment, participants were followed for 6 months to determine short-term CPAP adherence. Those with good short-term adherence were followed for an additional 6 months to explore long-term adherence and influencing factors. Short-term CPAP adherence rate was 33%. Being married or living with a partner, having an associate degree or baccalaureate degree or higher, and stronger health beliefs independently predicted short-term CPAP adherence. Only 25% of participants from the adherent group showed good long-term adherence. The factor associated with long-term CPAP adherence was participants not using alcohol. Adherence to CPAP is suboptimal among patients having OSA post-stroke. Addressing unfavorable predisposing factors and modifying health beliefs are suggested.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Cooperação do Paciente , Apneia Obstrutiva do Sono , Acidente Vascular Cerebral , Humanos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Pressão Positiva Contínua nas Vias Aéreas/psicologia , Pressão Positiva Contínua nas Vias Aéreas/estatística & dados numéricos , Masculino , Apneia Obstrutiva do Sono/psicologia , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/complicações , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Cooperação do Paciente/psicologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Idoso , China , Inquéritos e Questionários
5.
J Transl Med ; 21(1): 699, 2023 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-37805555

RESUMO

BACKGROUND: Epidemiological studies demonstrated that multiple amino acids (AAs) were associated with cardiovascular diseases (CVDs), but whether these associations were causal remains unclear. This study aims to investigate the causal relationships between circulating levels of 20 AAs and 10 CVDs in European and East Asian populations by Mendelian randomization (MR). METHODS: This MR study utilized single-nucleotide polymorphisms that were significantly associated with AAs as instrumental variables. Summary-level data for AAs and CVDs were obtained from public genome-wide association studies. The causal effects were primarily estimated by inverse variance weighting with multiplicative random effect method. Sensitivity analyses, including weighted median, weighted mode, and MR Egger regression, were used to test the robustness of our results. RESULTS: In the European population, alanine and serine were inversely associated with angina pectoris (AP) and chronic heart failure, respectively. With each unit increase of leucine, the risk of ischemic stroke increased by 10%. Moreover, tyrosine was positively associated with AP and deep vein thrombosis. In the East Asian population, each unit increase in glycine was associated with 4.1% and 9.0% decreased risks of coronary artery disease (CAD) and myocardial infarction (MI), respectively. A unit increase in serine was associated with 13.1%, 12.6% and 15.5% decreased risks of AP, CAD and MI, respectively. Sensitivity analyses supported the robustness of our results. CONCLUSIONS: This MR study demonstrated significant causal effects of circulating levels of AAs on CVDs, indicating the potential use of AAs as biomarkers or as therapeutic targets for CVD in clinical scenarios.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Infarto do Miocárdio , Humanos , Aminoácidos , Doenças Cardiovasculares/genética , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Angina Pectoris , Serina , Polimorfismo de Nucleotídeo Único/genética
6.
Thromb J ; 21(1): 28, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36918857

RESUMO

BACKGROUND: Risk prediction rules are important to establish appropriate treatment and management strategy for patients with different risk classification of pulmonary embolism (PE). Neutrophils are considered to be related to PE as an essential marker of inflammation. However, few studies have reported the association between neutrophil levels and risk classification of acute PE (APE). The aim of this study was to investigate the role of neutrophil levels upon admission in the assessment of risk classification of APE. METHODS: A total of 299 consecutive APE patients and 90 patients without APE confirmed by computed tomographic pulmonary angiography were retrospectively screened. APE patients were stratified into two subgroups according to clinical guidelines: low- (n = 233) and intermediate- and high-risk (n = 60) APE. RESULTS: The neutrophil levels in intermediate- and high-risk APE patients were significantly higher compared to low-risk APE or non-APE patients (P < 0.001). In multivariable logistic regression analysis, neutrophil levels were significantly and independently associated with intermediate- and high-risk APE (odds ratio = 1.239, 95% confidence interval [CI] 1.055-1.455, P = 0.009). Neutrophil levels were positively correlated with the pulmonary embolism severity index score (r = 0.357, P < 0.001), high sensitive C-reactive protein, D-dimer and pulmonary artery obstruction index (PAOI), in the overall population of APE patients. Receiver-operating characteristic curve analysis revealed that neutrophils had a better diagnostic value for intermediate- and high-risk APE (area under the curve [AUC] = 0.760, 95% CI 0.695-0.826; P < 0.001) compared to PAOI (AUC = 0.719) and D-dimer (AUC = 0.645). CONCLUSIONS: High neutrophil levels upon admission were significantly and independently associated with intermediate- and high-risk APE, which could be regarded as an indicator of inflammation and thrombosis in APE simultaneously. The potent diagnostic role of neutrophil levels and their competitive advantage over PAOI and D-dimer for the assessment of APE risk classification are suggested.

7.
J Appl Toxicol ; 43(2): 312-322, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35999056

RESUMO

Perfluorooctane sulfonate (PFOS) is a hepatotoxic environmental organic pollutant that can cause aberrant lipid accumulation in the liver. However, the molecular mechanism underlying PFOS-induced hepatic steatosis remains unclear. Our research showed that subchronic PFOS exposure inhibited AMP-activated protein kinase (AMPK) phosphorylation, leading to increased acetyl-CoA carboxylase (ACC) activity, attenuated fatty acid ß-oxidation, and consequent liver lipid accumulation. We found that 1 mg/kg/day PFOS exposure significantly aggravated steatosis in high-fat diet (HFD)-fed mice, along with reduced AMPK activity. Oil Red O results showed that PFOS exposure caused fat accumulation in HepG2 cells. As predicted, PFOS treatment reduced the level of phosphorylated AMPK in a concentration-dependent manner, leading to subsequent increase in ACC activity and lipid droplet accumulation in HepG2 cells. Treatment with 200-µM AMPK agonist AICAR alleviated PFOS-induced ACC activation and lipid accumulation. In summary, our data highlight a crucial role of AMPK/ACC pathway in PFOS-mediated liver lipid metabolic disorders.


Assuntos
Proteínas Quinases Ativadas por AMP , Fígado Gorduroso , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Metabolismo dos Lipídeos , Lipídeos
8.
Acta Pharmacol Sin ; 43(7): 1710-1720, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34848852

RESUMO

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD-PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO3), bicarbonate in superior vena cava (svcHCO3), and the partial pressure of dissolved CO2 gas in radial artery (aPCO2) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P < 0.05, except propionylcarnitine with P < 0.05 at T24). In contrast, galactinol dihydrate, guanosine monophosphate, and hydroxyphenylacetylglycine tended to decline at T24 and T48 (only galactinol dihydrate with P < 0.05 at T48). In conclusion, 17 metabolites that respond to shunt correction could be used as suitable noninvasive markers, and clinical measures, including DPAP, aHCO3, svcHCO3, and aPCO2, would be of great value in disease monitoring and evaluating future therapeutic interventions.


Assuntos
Cardiopatias Congênitas , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Bicarbonatos/uso terapêutico , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/cirurgia , Metabolômica , Período Perioperatório , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/cirurgia , Qualidade de Vida , Veia Cava Superior
9.
J Thromb Thrombolysis ; 53(4): 926-933, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34705198

RESUMO

The long-term prognosis of patients with chronic thromboembolic pulmonary hypertension (CTEPH) receiving different treatments is deserved to be analyzed in modern era of CTEPH treatment. From 2013 to 2019, a total of 364 patients diagnosed with CTEPH were retrospectively included, 14 patients were lost during follow-up. Among 350 patients included in the final analysis: 123 underwent pulmonary endarterectomy (PEA), 121 received balloon pulmonary angioplasty (BPA), and 106 treated with targeted drug alone. The median period of follow-up was 51.2 months, the estimated survival at 1-, 3-, 5- and 7-year was 97.1%, 93.3%, 86.9%, and 82.0% for the whole cohort; 100%, 99.20%, 96.5% and 92.5% in PEA group; 98.4%, 97.4%, 95.3% and 89.3% in BPA group;92.5%, 81.9%, 70.1% and 66.8% in patients who received targeted drug alone. In comparing with targeted treatment along, results of multivariate Cox analysis after adjusting the confounders showed that receiving PEA decreased the risk of death by 83% (HR [hazard ratio] 0.17, 95% CI [Confidence interval] 0.07-0.44) and receiving BPA decreased the risk of death by 89% (HR 0.11, 95% CI 0.04-0.29). In conclusion, the estimated survival of CTEPH patients at 1-, 3-, 5- and 7-year was 97.1%, 93.3%, 86.9%, and 82.0% respectively. The intervention of revascularization, including PEA and BPA, were preferred than treating with targeted drug alone in the view of long-term prognosis of CTEPH.


Assuntos
Angioplastia com Balão , Hipertensão Pulmonar , Embolia Pulmonar , Angioplastia com Balão/métodos , Doença Crônica , Endarterectomia/métodos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/cirurgia , Artéria Pulmonar/cirurgia , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Estudos Retrospectivos
10.
J Appl Toxicol ; 42(5): 806-817, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34687223

RESUMO

Perfluorooctane sulfonate (PFOS) is a fluorinated organic pollutant with substantial accumulation in mammalian liver tissues. However, the impact of chronic PFOS exposure on liver disease progression and the underlying molecular mechanisms remain elusive. Herein, we for the first time revealed that micromolar range of PFOS exposure initiates the activation of NLR pyrin domain containing 3 (NLRP3) inflammasome to drive hepatocyte pyroptosis. We showed that 5 mg/kg/day PFOS exposure may exacerbated liver inflammation and steatosis in high-fat diet (HFD)-fed mice with concurrently elevated expression of NLRP3 and caspase-1. PFOS exposure resulted in viability impairment and LDH release in BRL-3A rat liver cells. 25-100 µM concentrations of PFOS exposure activated the NLRP3 inflammasome, leading to consequent GSDMD cleavage, IL-1ß release and the initiation of pyroptosis in a dose-dependent manner, whereas treatment with 10 µM NLRP3 inhibitor MCC950 abrogated this effect. Moreover, pretreatment of 5 mM ROS scavenger N-acetyl-L-cysteine (NAC) ameliorated PFOS-induced NLRP3 inflammasome activation and pyroptosis. Collectively, our data highlight a pivotal role of pyroptotic death in PFOS-mediated liver inflammation and metabolic disorder.


Assuntos
Inflamassomos , Piroptose , Ácidos Alcanossulfônicos , Animais , Fluorocarbonos , Hepatócitos , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Fígado/metabolismo , Mamíferos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Espécies Reativas de Oxigênio/metabolismo
11.
Environ Toxicol ; 37(5): 983-994, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34990082

RESUMO

Perfluorooctane sulfonate (PFOS) is a widespread environmental pollutant and may cause a variety of adverse health effects. The hepatotoxicity of PFOS has attracted particular attention, given the fact that the liver has one of the highest PFOS accumulations among human tissues. In this study, we revealed that subchronic PFOS exposure may exacerbate carbon tetrachloride (CCl4 )-induced liver fibrosis in animal models. Administration with 1 mg/kg PFOS every other day for 56 days dramatically enhanced CCl4 -mediated liver injury and hepatic stellate cell (HSC) activation. Furthermore, PFOS exposure may promote the activation of high-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4) signaling pathway through inducing the secretion of HMGB1 from hepatocytes. PFOS exposure induced the translocation of HMGB1 from the nucleus into the cytoplasm of hepatocytes and cultured BRL-3A cells at a starting concentration of 50 µM. This process is accompanied with concurrent flux of calcium, suggesting a link between calcium signaling and HMGB1 release following PFOS exposure. Finally, we showed that PFOS-exposed conditional medium (PFOS-CM) of hepatocytes may induce the translocation of Smad2/3 in HSCs in a TLR4-dependent manner. Taken together, subchronic PFOS exposure might play a pro-fibrotic role via a HMGB1/TLR4-dependent Smad signaling in HSCs. Our findings for the first time uncovered an involvement of PFOS exposure in liver fibrosis via HMGB1/TLR4/Smad signaling.


Assuntos
Proteína HMGB1 , Receptor 4 Toll-Like , Ácidos Alcanossulfônicos/toxicidade , Animais , Fluorocarbonos/toxicidade , Proteína HMGB1/metabolismo , Células Estreladas do Fígado , Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
12.
Theor Biol Med Model ; 18(1): 6, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468179

RESUMO

BACKGROUND: The effects of arterial wall compliance on blood flow have been revealed using fluid-structure interaction in last decades. However, microcirculation is not considered in previous researches. In fact, microcirculation plays a key role in regulating blood flow. Therefore, it is very necessary to involve microcirculation in arterial hemodynamics. OBJECTIVE: The main purpose of the present study is to investigate how wall compliance affects the flow characteristics and to establish the comparisons of these flow variables with rigid wall when microcirculation is considered. METHODS: We present numerical modeling in arterial hemodynamics incorporating fluid-structure interaction and microcirculation. A novel outlet boundary condition is employed to prescribe microcirculation in an idealised model. RESULTS: The novel finding in this work is that wall compliance under the consideration of microcirculation leads to the increase of wall shear stress in contrast to rigid wall, contrary to the traditional result that wall compliance makes wall shear stress decrease when a constant or time dependent pressure is specified at an outlet. CONCLUSIONS: This work provides the valuable study of hemodynamics under physiological and realistic boundary conditions and proves that wall compliance may have a positive impact on wall shear stress based on this model. This methodology in this paper could be used in real model simulations.


Assuntos
Hemodinâmica , Modelos Cardiovasculares , Simulação por Computador , Microcirculação , Estresse Mecânico
13.
J Surg Oncol ; 123 Suppl 1: S25-S29, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33730378

RESUMO

BACKGROUND AND OBJECTIVES: In 2016, the self-pulling and latter transection method (named "Delta SPLT"), a modified delta-shaped gastroduodenostomy (DA) technique for totally laparoscopic distal gastrectomy, was described. Delta SPLT reduced the technical difficulty of the surgery and the quantity of cartridges required with a manageable initial safety profile. Here, the safety and feasibility of this technique are analyzed at 1 year's follow-up. METHODS: The demographic and clinicopathologic profiles, perioperative details, and postoperative outcomes of 45 consecutive patients who underwent Delta SPLT from March 2016 to March 2019 were retrospectively analyzed. The Delta SPLT technique, which consisted of one endoscopic linear stapler and four cartridges each, was used for reconstruction in every case. RESULTS: The mean operative time was 127.1 ± 38.2 min, including a reconstruction duration of 22.6 ± 7.2 min. There were no surgical or anastomotic complications. The mean postoperative stay duration was 5.8 ± 1.2 days, and the morbidity rate was 2.2% with one case of postoperative pneumonia. CONCLUSIONS: The results at the one-year follow-up suggest that Delta SPLT is a safe and feasible procedure. Delta SPLT is characterized by fewer difficulties experienced during surgery, lower surgical costs, it is easy to practice, and it is beneficial for patients who are undergoing gastroduodenostomy.


Assuntos
Gastroenterostomia/métodos , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Duodeno/cirurgia , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Gastroenterostomia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
14.
J Enzyme Inhib Med Chem ; 35(1): 1372-1378, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32571102

RESUMO

Gut microbial ß-glucuronidase (GUS) is a potential therapeutic target to reduce gastrointestinal toxicity caused by irinotecan. In this study, the inhibitory effects of 17 natural cinnamic acid derivatives on Escherichia coli GUS (EcGUS) were characterised. Seven compounds, including caffeic acid ethyl ester (CAEE), had a stronger inhibitory effect (IC50 = 3.2-22.2 µM) on EcGUS than the positive control, D-glucaric acid-1,4-lactone. Inhibition kinetic analysis revealed that CAEE acted as a competitive inhibitor. The results of molecular docking analysis suggested that CAEE bound to the active site of EcGUS through interactions with Asp163, Tyr468, and Glu504. In addition, structure-activity relationship analysis revealed that the presence of a hydrogen atom at R1 and bulky groups at R9 in cinnamic acid derivatives was essential for EcGUS inhibition. These data are useful to design more potent cinnamic acid-type inhibitors of EcGUS.


Assuntos
Cinamatos/farmacologia , Inibidores Enzimáticos/farmacologia , Escherichia coli/enzimologia , Glucuronidase/antagonistas & inibidores , Cinamatos/química , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
15.
PLoS Genet ; 12(9): e1006259, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27617961

RESUMO

MicroRNA-22 (miR-22) is emerging as a critical regulator in organ development and various cancers. However, its role in normal hematopoiesis and leukaemogenesis remains unclear. Here, we detected its increased expression during monocyte/macrophage differentiation of HL-60, THP1 cells and CD34+ hematopoietic stem/progenitor cells, and confirmed that PU.1, a key transcriptional factor for monocyte/macrophage differentiation, is responsible for transcriptional activation of miR-22 during the differentiation. By gain- and loss-of-function experiments, we demonstrated that miR-22 promoted monocyte/macrophage differentiation, and MECOM (EVI1) mRNA is a direct target of miR-22 and MECOM (EVI1) functions as a negative regulator in the differentiation. The miR-22-mediated MECOM degradation increased c-Jun but decreased GATA2 expression, which results in increased interaction between c-Jun and PU.1 via increasing c-Jun levels and relief of MECOM- and GATA2-mediated interference in the interaction, and thus promoting monocyte/macrophage differentiation. We also observed significantly down-regulation of PU.1 and miR-22 as well as significantly up-regulation of MECOM in acute myeloid leukemia (AML) patients. Reintroduction of miR-22 relieved the differentiation blockage and inhibited the growth of bone marrow blasts of AML patients. Our results revealed new function and mechanism of miR-22 in normal hematopoiesis and AML development and demonstrated its potential value in AML diagnosis and therapy.


Assuntos
Proteínas de Ligação a DNA/genética , Fator de Transcrição GATA2/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas/biossíntese , Proto-Oncogenes/genética , Transativadores/biossíntese , Fatores de Transcrição/genética , Diferenciação Celular/genética , Regulação Neoplásica da Expressão Gênica , Células HL-60 , Hematopoese/genética , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucemia Mieloide Aguda/patologia , Proteína do Locus do Complexo MDS1 e EVI1 , Macrófagos/metabolismo , MicroRNAs/biossíntese , Monócitos/metabolismo , Proteínas Proto-Oncogênicas/genética , Transativadores/genética
16.
J Biol Phys ; 45(2): 183-192, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31062132

RESUMO

To strengthen the detailed understanding of arterial stenosis, we construct a novel hemodynamic model. Frequently used symmetric stenosis is employed in this work. Being different from a traditional model, this numerical model adopts microcirculation resistance as an outlet boundary condition, which is called a seepage condition. Meanwhile, fluid-structure interactions are used in the numerical simulation considering the interrelationship of blood and arterial wall. Our results indicate that (i) the region upstream of stenosis experiences very high pressures during cardiac cycles, (ii) pressure drops much faster as the flow moves into the stenotic region, and (iii) high flow velocities and high shear stresses occur in the post-stenosis region. This work provides evidence that there is a strong effect of the function of microcirculation on stenosis. This contributes to evaluating potential stenotic behavior in arteries and is pivotal in guiding disease treatment.


Assuntos
Artérias/fisiopatologia , Constrição Patológica/fisiopatologia , Hemodinâmica , Modelos Biológicos , Pressão , Estresse Mecânico
17.
Appl Opt ; 57(20): 5623-5627, 2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-30118073

RESUMO

To study the four-wave mixing (FWM) effect and wavelength conversion in a hollow core bandgap photonic crystal fiber filled with Ar, we conducted an experiment using a femtosecond laser with the pulse width of 120 fs, a repetition rate of 76 MHz, and tunable central wavelength from 760 to 980 nm. It is observed that new spectra are generated in both sides of the pump at a special wavelength, which can exactly satisfy the phase matching conditions of FWM. Combining experimental results with theoretical analysis, we find that the experimental phenomenon is mainly caused by FWM, and some other nonlinear phase effects, such as self-phase modulation, stimulated Raman scattering, and the soliton effect, have also occurred in this nonlinear process.

18.
Molecules ; 23(12)2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30467293

RESUMO

Cytisine-pterocarpan-derived compounds were biomimetically synthesized with (-)-cytisine and (-)-maackiain via a N,N-4-dimethyl-4-aminopyridine (DMAP)-mediated synthetic strategy in a mild manner. In the present study, tonkinensine B (4) was elaborated in good and high yields with the optimized reaction conditions. The in vitro cytotoxicity of compound 4 was evaluated against breast cancer cell lines and showed that 4 had a better cytotoxicity against MDA-MB-231 cells (IC50 = 19.2 µM). Depending on the research on cytotoxicities of 4 against RAW 264.7 and BV2 cells, it was suggested that 4 produced low cytotoxic effects on the central nervous system. Further study indicated that 4 demonstrated cytotoxic activity against MDA-MB-231 cells and the cytotoxic activity was induced by apoptosis. The results implied that the apoptosis might be induced by mitochondrion-mediated apoptosis via regulating the ratio of Bax/Bcl-2 and promoting the release of cytochrome c from the mitochondrion to the cytoplasm in MDA-MB-231 cells.


Assuntos
Neoplasias da Mama/metabolismo , Citocromos c/metabolismo , Compostos Heterocíclicos com 2 Anéis/síntese química , Compostos Heterocíclicos com 2 Anéis/farmacologia , Mitocôndrias/metabolismo , Alcaloides/química , Animais , Azocinas/química , Mimetismo Biológico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Compostos Heterocíclicos com 2 Anéis/química , Humanos , Células MCF-7 , Camundongos , Estrutura Molecular , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pterocarpanos/química , Quinolizinas/química , Células RAW 264.7 , Proteína X Associada a bcl-2/metabolismo
19.
Cell Mol Neurobiol ; 37(6): 1009-1019, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27817168

RESUMO

DIX domain containing 1 (DIXDC1), the human homolog of coiled-coil-DIX1 (Ccd1), is a positive regulator of Wnt signaling pathway. Recently, it was found to act as a candidate oncogene in colon cancer, non-small-cell lung cancer, and gastric cancer. In this study, we aimed to investigate the clinical significance of DIXDC1 expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that DIXDC1 was overexpressed in glioma tissues and glioma cell lines. The expression level of DIXDC1 was evidently linked to glioma pathological grade and Ki-67 expression. Kaplan-Meier curve showed that high expression of DIXDC1 may lead to poor outcome of glioma patients. Serum starvation and refeeding assay indicated that the expression of DIXDC1 was associated with cell cycle. To determine whether DIXDC1 could regulate the proliferation and migration of glioma cells, we transfected glioma cells with interfering RNA-targeting DIXDC1; investigated cell proliferation with Cell Counting Kit (CCK)-8, flow cytometry assays, and colony formation analyses; and investigated cell migration with wound healing assays and transwell assays. According to our data, knockdown of DIXDC1 significantly inhibited proliferation and migration of glioma cells. These data implied that DIXDC1 might participate in the development of glioma, suggesting that DIXDC1 can become a potential therapeutic strategy for glioma.


Assuntos
Neoplasias Encefálicas/patologia , Movimento Celular , Técnicas de Silenciamento de Genes , Glioma/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas dos Microfilamentos/metabolismo , Adulto , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Regulação para Cima
20.
Surg Endosc ; 31(7): 2968-2976, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27826782

RESUMO

BACKGROUND: This study depicts a novel reconstruction method of self-pulling and latter transection (SPLT) in totally laparoscopic total gastrectomy (TLTG) and evaluates its feasibility and short-term safety by comparing its surgical and postoperative outcomes with the conventional TLTG. PATIENTS AND METHODS: Forty patients with gastric cancer from June 2014 to December 2015 received SPLT-TLTG. Data of clinicopathologic characteristics, surgical and postoperative outcomes, and follow-up findings in SPLT cases were collected and retrospectively compared with those of conventional TLTG to clarify the clinical benefits. RESULTS: The mean duration of the operation was 179.5 ± 37.7 min in SPLT-TLTG, including 23.2 ± 8.8 min of reconstruction; both were significantly shorter than the conventional TLTG (P = 0.030; P < 0.001). There were no significant differences in blood loss, time of the first flatus and postoperative hospital stays between two groups. SPLT-TLTG developed no complication beyond the conventional TLTG. CONCLUSION: SPLT-TLTG is safe, feasible and minimally invasive. It may serve as a promising procedure for gastric cancer that helps to expand the indication of TLTG to cases with even high level of tumor invasion and requires less in both surgical skills and clinical costs.


Assuntos
Gastrectomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos
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