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1.
Proc Natl Acad Sci U S A ; 121(6): e2318174121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38289955

RESUMO

Atomically dispersed catalysts are a promising alternative to platinum group metal catalysts for catalyzing the oxygen reduction reaction (ORR), while limited durability during the electrocatalytic process severely restricts their practical application. Here, we report an atomically dispersed Co-doped carbon-nitrogen bilayer catalyst with unique dual-axial Co-C bonds (denoted as Co/DACN) by a smart phenyl-carbon-induced strategy, realizing highly efficient electrocatalytic ORR in both alkaline and acidic media. The corresponding half-wave potential for ORR is up to 0.85 and 0.77 V (vs. reversible hydrogen electrode (RHE)) in 0.5 M H2SO4 and 0.1 M KOH, respectively, representing the best ORR activity among all non-noble metal catalysts reported to date. Impressively, the Zn-air battery (ZAB) equipped with Co/DACN cathode achieves outstanding durability after 1,688 h operation at 10 mA cm-2 with a high current density (154.2 mA cm-2) and a peak power density (210.1 mW cm-2). Density functional theory calculations reveal that the unique dual-axial cross-linking Co-C bonds of Co/DACN significantly enhance the stability during ORR and also facilitate the 4e- ORR pathway by forming a joint electron pool due to the improved interlayer electron mobility. We believe that axial engineering opens a broad avenue to develop high-performance heterogeneous electrocatalysts for advanced energy conversion and storage.

2.
BMC Genomics ; 25(1): 628, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914980

RESUMO

BACKGROUND: Peritoneal carcinomatosis was the main reason leading to gastric cancer (GC)-related death. We aimed to explore the roles of dysregulated microRNAs (miRNAs) and related immune regulation activities in GC-associated malignant ascites. METHODS: GSE126399 were downloaded from GEO database. Differentially expressed miRNAs in GC ascites samples was firstly screened, and critical miRNAs were further investigated by LASSO (least absolute shrinkage and selection operator) logistic regression and random forest (RF) algorithm. Receiver operating characteristic of critical miRNAs was also constructed. Moreover, functional analysis, immune cell infiltration associated with differentially expressed mRNAs were further analyzed. After selecting key modules by weighted gene co-expression network analysis, mRNAs related with survival performance and transcription factor (TF)-miRNA-mRNA network were constructed. RESULTS: Hsa-miR-181b-5p was confirmed as critical differentially expressed miRNAs in GC ascites. Then, the tumor samples were divided into high- and low- expression groups divided by mean expression levels of hsa-miR-181b-5p, and subjects with high hsa-miR-181b-5p levels had better survival outcomes. In total, 197 differentially expressed mRNAs associated with hsa-miR-181b-5p levels were obtained, and these mRNAs were mainly enriched in muscle activity and vascular smooth muscle contraction. Hsa-miR-181b-5 was positively related with activated CD4 T cells and negatively related with eosinophil. 17 mRNAs were selected as mRNAs significantly related with prognosis of GC, such as PDK4 and RAMP1. Finally, 75 TF-miRNA-mRNA relationships were obtained, including 15 TFs, hsa-miR-181b-5p, and five mRNAs. CONCLUSION: Our data suggest that the differentially expressed hsa-miR-181b-5p in ascites samples of GC patients may be a valuable prognostic marker and a potential target for therapeutic intervention, which should be validated in the near future.


Assuntos
Ascite , Biomarcadores Tumorais , MicroRNAs , Neoplasias Gástricas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Ascite/genética , Ascite/metabolismo , Ascite/patologia , Prognóstico , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
3.
Clin Nephrol ; 100(3): 99-106, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37485879

RESUMO

AIMS: This study aims to investigate the relationship of blood pressure (BP) and systolic BP (SBP) variability with residual kidney function (RKF) loss in hemodialysis (HD) patients. MATERIALS AND METHODS: The demographic and clinical information and data on RKF loss events in HD patients were collected. The baseline characteristics of the patients were compared among groups according to pre- and postdialysis SBP (< 120, 120 - 139, 140 - 159, and ≥ 160 mmHg) and diastolic BP (DBP) (< 80, 80 - 89, 90 - 99, and ≥ 1 00 mmHg). Participants were divided into two groups based on the mean intradialytic and interdialytic SBP variability. Kaplan-Meier analysis and Cox regression analysis were used to evaluate the risk of RKF loss. RESULTS: A total of 157 participants with an average HD vintage of 35.97 months were included. The group with the lowest predialysis SBP showed the longest duration of residual urine. However, Kaplan-Meier analysis and Cox regression analysis indicated that BP and SBP variability were not independent risk factors for RKF loss. Higher serum albumin levels showed protective effects against RKF loss, and diabetes mellitus (DM) and higher serum calcium were the independent risk factors for RKF loss. CONCLUSION: BP and SBP variability were not independent risk factors for RKF loss in HD patients. DM, serum albumin, and calcium were independent factors related to RKF loss.


Assuntos
Falência Renal Crônica , Humanos , Pressão Sanguínea/fisiologia , Falência Renal Crônica/etiologia , Cálcio , Diálise Renal/efeitos adversos , Rim
4.
Opt Lett ; 47(21): 5453-5456, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37219242

RESUMO

The sensitivity of incoherent optical methods using video cameras (e.g., optical flow and digital image correlation) for full-field displacement measurements, defined by the minimum measurable displacements, is essentially limited by the finite bit depth of the digital camera due to the quantization with round-off error. Quantitatively, the theoretical sensitivity limit is determined by the bit depth B as δp = 1/(2B - 1) [pixel] which corresponds to a displacement causing an intensity change of one gray level. Fortunately, the random noise in the imaging system may be leveraged to perform a natural dithering to overcome the quantization, rendering the possibility of breaking the sensitivity limit. In this work we study such a theoretical sensitivity limit and present a spatiotemporal pixel-averaging method with dithering to achieve super-sensitivity. The numerical simulation results indicate that super-sensitivity can be achieved and is quantitatively determined by the total pixel number N for averaging and the noise level σn as δ p ∗∝(σ n /N)δ p.

5.
Ecotoxicol Environ Saf ; 231: 113212, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35065501

RESUMO

Light, one of the most important natural resources for plant species, significantly influences the biomass yield and nutrient uptake capacity in plants. Light sources with different spectra combinations can impact the bioavailability, toxicity, and solubility of heavy metals in soils by altering the concentrations and fractionations of soil dissolved organic matter (DOM). A series of light irradiation treatments were performed to evaluate the influence of red, yellow, and blue lights on the characteristics of DOM in the rhizosphere soils of Arabidopsis thaliana. The results showed that monochromatic red light significantly raised the levels of DOM and proportions of hydrophilic fractionations in the rhizosphere of A. thaliana relative to the control, while monochromatic blue light had the opposite effect. Moreover, the proportions of hydrophobic acid, which can mobilize Cd effectively, also raised with increasing doses of red light, which stimulated Cd mobilization. The application of yellow light not only increased the levels of hydrophobic acid in monochromatic red light treatment but also decreased the proportion of hydrophobic fractions in monochromatic blue light treatment, partially weakening the negative impacts of pure blue light on soil Cd activation. Moreover, DOM from the combined red, yellow, and blue lights resulted in a significantly stronger Cd extraction efficiency than the other light irradiation treatments, consequently enhancing the Cd phytoextraction efficiency of A. thaliana. The findings of this study demonstrated that a suitable light combination could enhance the phytoremediation effect of A. thaliana by activating soil Cd, and this method can be extrapolated to the real field, where light irradiation can be easily applied and modulated.


Assuntos
Arabidopsis , Poluentes do Solo , Biodegradação Ambiental , Cádmio/análise , Matéria Orgânica Dissolvida , Rizosfera , Solo , Poluentes do Solo/análise
6.
J Card Surg ; 37(8): 2285-2291, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35526149

RESUMO

OBJECTIVES: Tetralogy of Fallot (TOF) is the most common deformity combined with the unilateral absence of the mediastinal pulmonary artery (UAMPA), and its treatment strategy remains controversial. In this study, we analyzed the effect of bilateral pulmonary reconstruction in patients with TOF combined with UAMPA. METHODS: This was a single-center, retrospective review of 1713 patients with TOF between January 2009 and November 2021. Overall, eight patients were diagnosed with TOF combined with UAMPA. Among them, seven underwent surgery: three underwent one-stage TOF correction with bilateral pulmonary artery reconstruction; three patients underwent bilateral pulmonary artery reconstruction, followed by two-stage TOF correction after several months; and one patient underwent two procedures of left pulmonary artery reconstruction, and the ventral septal defect remained open. The left pulmonary arteries were reconstructed with a Goretex conduit in three cases, direct anastomosis in two cases, and the modified autologous tissue extension technique in two cases. RESULTS: All seven patients survived during the postoperative follow-up and showed good cardiac function and normal oxygen saturation of >97%. During follow-up echocardiography, we noted that the left pulmonary arteries reconstructed with a Goretex conduit or direct anastomosis had thrombosis or stenosis. However, those reconstructed using the modified autologous tissue extension technique was unobstructed. CONCLUSIONS: In patients with TOF and UAMPA, if there is a pulmonary artery confluence in the affected hilum, it is feasible to implement bilateral pulmonary artery reconstruction for one-stage TOF correction. The use of the pulmonary artery extension technique and autologous tissue for bilateral pulmonary reconstruction could reduce the incidence of anastomotic stenosis.


Assuntos
Cardiopatias Congênitas , Tetralogia de Fallot , Constrição Patológica , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Politetrafluoretileno , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Estudos Retrospectivos , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/cirurgia
7.
Angew Chem Int Ed Engl ; 61(11): e202110186, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490688

RESUMO

Studying structure-activity correlations of electrocatalysts is essential for improving the conversion of electrical to chemical energy. Recently, increasing evidence obtained by operando characterization techniques reveal that the structural evolution of catalysts caused by the interplay with electric fields, electrolytes and reactants/intermediates brings about the formation of real active sites. Hence, it is time to summarize structural evolution related research advances and envisage future developments. In this Minireview, we first introduce the fundamental concepts associated with structural evolution (e.g., catalysts, active sites/centers and stability/lifetime) and their relevance. Then, the multiple triggers of structural evolution and advanced operando characterizations are discussed. Significantly, a brief overview of structural evolution and its reversibility in heterogeneous electrocatalysis is provided, especially for the representative electrocatalytic oxygen evolution reaction (OER) and CO2 reduction reaction (CO2 RR) processes. Lastly, key challenges and opportunities in this exciting field are highlighted.

8.
Int Heart J ; 62(1): 127-134, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33455984

RESUMO

Mutations in the sarcomeric protein filamin C (FLNC) gene have been linked to hypertrophic cardiomyopathy (HCM), as they have been determined to increase the risk of ventricular arrhythmia and sudden death. Thus, in this study, we identified a novel missense mutation of FLNC in a Chinese family with HCM, and, interestingly, a second novel truncating mutation of MYLK2 was discobered in one family member with different phenotype.We performed whole-exome sequencing in a Chinese family with HCM of unknown cause. To determine and confirm the function of a novel mutation of FLNC, we introduced the mutant and wild-type gene into AC16 cells (human cardiomyocytes): we then used western blotting to analyze the expression of FLNC in subcellular fractions, and confocal microscope to observe the subcellular distribution of the protein.As per our findings, we were able to identify a novel missense single nucleotide variant (FLNC c.G5935A [p.A1979T]) in the family, which segregates with the disease. FLNC expression levels were observed to be equivalent in both wild-type and p.A1979T cardiomyocytes. However, the expression of the mutant protein has resulted in cytoplasmic protein aggregations, in contrast to wild-type FLNC, which was distributed in the cytoplasm and did not form aggregates. Unexpectedly, a second truncating mutation, NM_033118:exon8:c.G1138T:p.E380X of the MYLK2 gene, was identified in the mother of the proband with dilated cardiomyopathy, which was not found in other subjects.We then identified the FLNC A1979T mutation as a novel pathogenic variant associated with HCM in a Chinese family as well as a second causal mutation in a family member with a distinct phenotype. The possibility that there is more than one causal mutation in cardiomyopathy warrants clinical attention, especially for patients with atypical clinical features.


Assuntos
Povo Asiático/genética , Proteínas de Ligação ao Cálcio/genética , Cardiomiopatias/genética , Filaminas/genética , Quinase de Cadeia Leve de Miosina/genética , Adulto , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Cardiomiopatia Dilatada/genética , Cardiomiopatia Hipertrófica/genética , Morte Súbita Cardíaca/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Mutação de Sentido Incorreto/genética , Miócitos Cardíacos/ultraestrutura , Linhagem , Fenótipo , Fatores de Risco , Fibrilação Ventricular/epidemiologia , Fibrilação Ventricular/mortalidade , Sequenciamento do Exoma/métodos
9.
Sensors (Basel) ; 20(12)2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32580321

RESUMO

Video-based techniques for identification of structural dynamics have the advantage that they are very inexpensive to deploy compared to conventional accelerometer or strain gauge techniques. When structural dynamics from video is accomplished using full-field, high-resolution analysis techniques utilizing algorithms on the pixel time series such as principal components analysis and solutions to blind source separation the added benefit of high-resolution, full-field modal identification is achieved. An important property of video of vibrating structures is that it is particularly sparse. Typically video of vibrating structures has a dimensionality consisting of many thousands or even millions of pixels and hundreds to thousands of frames. However the motion of the vibrating structure can be described using only a few mode shapes and their associated time series. As a result, emerging techniques for sparse and random sampling such as compressive sensing should be applicable to performing modal identification on video. This work presents how full-field, high-resolution, structural dynamics identification frameworks can be coupled with compressive sampling. The techniques described in this work are demonstrated to be able to recover mode shapes from experimental video of vibrating structures when 70% to 90% of the frames from a video captured in the conventional manner are removed.

10.
J Gene Med ; 21(4): e3070, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30659708

RESUMO

INTRODUCTION: Cardiac septal defects account for more than 50% of congenital heart defects. Ankyrin repeat domain 1 (ANKRD1) is an important transcription factor that is mutated in multiple cardiac diseases; however, a relationship between the ANKRD1 mutation and cardiac septal defects has not been described. METHODS: We examined genetic mutations in a large family with three cardiac septal defect patients. Whole exome sequencing, bioinformatics and conservation analysis were utilized to predict the pathogenicity of candidate mutations. Dual luciferase reporter assay and nuclear localization experiments were performed to evaluate the influence of target mutation. RESULTS: A heterozygous, missense variant of ANKRD1 (MIM* 609599): NM_014391: exon6: c.C560T:p.S187F was identified at a highly conserved region. Sanger sequencing in extended family members demonstrated an incomplete inheritance model. When co-activated with NKX2.5, ANKRD1 repressed ANF expression as assessed by a dual-luciferase reporter assay, and p.S187F mutation enhanced the repressive effect (0.318 ± 0.018 versus 0.564 ± 0.048, p < 0.01). A real-time polymerase chain reaction confirmed that p.S187F mutation of ANKRD1 decreased the expression of endogenous ANF (0.85 ± 0.05 versus 0.61 ± 0.04, p < 0.01). Furthermore, nuclear localization experiments demonstrated that the mutation significantly decreased the nuclear distribution of ANKRD1. CONCLUSIONS: The present study is the first to identify the p.S187F mutant of ANKRD1, which is associated with cardiac septal defects.


Assuntos
Repetição de Anquirina/genética , Defeitos dos Septos Cardíacos/genética , Proteínas Musculares/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Sequência de Aminoácidos , Linhagem Celular , Feminino , Regulação da Expressão Gênica/genética , Células HEK293 , Cardiopatias Congênitas/genética , Humanos , Lactente , Masculino , Mutação/genética
11.
Prenat Diagn ; 38(6): 406-413, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29573438

RESUMO

OBJECTIVES: This study aimed to determine chromosomal abnormalities and copy number variations (CNVs) in fetuses with congenital heart disease (CHD) by chromosomal microarray analysis (CMA). METHODS: One hundred and ten cases with CHD detected by prenatal echocardiography were enrolled in the study; 27 cases were simple CHDs, and 83 were complex CHDs. Chromosomal microarray analysis was performed on the Affymetrix CytoScan HD platform. All annotated CNVs were validated by quantitative PCR. RESULTS: Chromosomal microarray analysis identified 6 cases with chromosomal abnormalities, including 2 cases with trisomy 21, 2 cases with trisomy 18, 1 case with trisomy 13, and 1 unusual case of mosaic trisomy 21. Pathogenic CNVs were detected in 15.5% (17/110) of the fetuses with CHDs, including 13 cases with CHD-associated CNVs. We further identified 10 genes as likely novel CHD candidate genes through gene functional enrichment analysis. We also found that pathogenic CMA results impacted the rate of pregnancy termination. CONCLUSIONS: This study shows that CMA is particularly effective for identifying chromosomal abnormalities and CNVs in fetuses with CHDs as well as having an effect on obstetrical outcomes. The elucidation of the genetic basis of CHDs will continue to expand our understanding of the etiology of CHDs.


Assuntos
Aberrações Cromossômicas , Cardiopatias Congênitas/diagnóstico , Análise em Microsséries , Diagnóstico Pré-Natal/métodos , Adulto , Análise Citogenética , Variações do Número de Cópias de DNA , Feminino , Cardiopatias Congênitas/genética , Humanos , Gravidez
12.
Chem Pharm Bull (Tokyo) ; 66(4): 439-451, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29607910

RESUMO

The novel hydroxamates containing purine scaffold were designed, synthesized and screened for their biological activities as histone deacetylase (HDAC) inhibitors. Some of them exhibited excellent acti-HDACs activities and antiproliferative activities, the most promising compound was 7m'. Western blot analysis indicated the compounds 7f', 7l', 7m', 7o' could increase histone H3 acetylation levels in HCT116 and K562 cell lines, and 7m' increased the level of acetyl histone H3 in a dose-dependent manner, which is similar to the behavior of suberoylanilide hydroxamic acid (SAHA). Molecular docking study revealed that the conformation of 7m' in the active site of HDAC2 was similar to positive drug SAHA, which were oriented with the hydroxamic acid towards the catalytic center and formed metal binding with zinc ion.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Ácidos Hidroxâmicos/farmacologia , Purinas/farmacologia , Relação Dose-Resposta a Droga , Células HCT116 , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Ácidos Hidroxâmicos/síntese química , Ácidos Hidroxâmicos/química , Células K562 , Simulação de Acoplamento Molecular , Estrutura Molecular , Purinas/química , Relação Estrutura-Atividade
13.
Opt Express ; 24(6): 6004-10, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27136794

RESUMO

We propose, fabricate and demonstrate on-chip photonic integration of suspended InGaN/GaN multiple quantum wells (MQWs) devices on the GaN-on-silicon platform. Both silicon removal and back wafer etching are conducted to obtain membrane-type devices, and suspended waveguides are used for the connection between p-n junction InGaN/GaN MQWs devices. As an in-plane data transmission system, the middle p-n junction InGaN/GaN MQWs device is used as a light emitting diode (LED) to deliver signals by modulating the intensity of the emitted light, and the other two devices act as photodetectors (PDs) to sense the light guided by the suspended waveguide and convert the photons into electrons, achieving 1 × 2 in-plane information transmission via visible light. Correspondingly, the three devices can function as independent PDs to realize multiple receivers for free space visible light communication. Further, the on-chip photonic platform can be used as an active electro-optical sensing system when the middle device acts as a PD and the other two devices serve as LEDs. The experimental results show that the auxiliary LED sources can enhance the amplitude of the induced photocurrent.

14.
J Vasc Surg ; 64(5): 1468-1477, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26527422

RESUMO

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a persistent elevation of pulmonary artery pressure and ventricular hypertrophy. Tetrandrine is a bisbenzylisoquinoline alkaloid that can decrease blood pressure, inhibit the proliferation of vascular smooth muscle cells, and block cardiac hypertrophy, but whether it has a therapeutic effect on PAH remains poorly defined. This study was undertaken to investigate the efficacy of tetrandrine on PAH. METHODS: Forty-eight male Sprague-Dawley rats were randomly and equally divided into four groups. The control group was injected with normal saline; the others were injected with monocrotaline (MCT) to induce PAH, then treated with saline, tetrandrine, and vardenafil, respectively, from day 21 to day 42. On day 43, we measured the mean pulmonary artery pressure under general anesthesia, dissected the rat, and calculated the right ventricular hypertrophy index [right ventricle/(left ventricle plus septum)]. Later we observed the changes in the pulmonary vascular wall; measured the expression of cyclic guanosine monophosphate-dependent protein kinase type 1 and inducible nitric oxide synthase; measured the levels of superoxide dismutase, glutathione, malondialdehyde, and catalase; and then compared the results among groups. RESULTS: Compared with the MCT group, rats treated with tetrandrine had attenuated mean pulmonary artery pressure (20.48 ± 1.49 vs 30.07 ± 1.51; P < .01) and right ventricular hypertrophy index (49.19 ± 2.45 vs 68.50 ± 1.95; P < .01), inhibited proliferation of pulmonary artery smooth muscle cells, and improved endothelial function. Tetrandrine also upregulated the expression of protein kinase type 1 (90.86 ± 1.95 vs 67.34 ± 1.50; P < .01); downregulated the expression of inducible nitric oxide synthase (74.76 ± 1.48 vs 80.19 ± 0.28; P < .01); increased levels of superoxide dismutase (245.54 ± 12.98 vs 166.16 ± 21.42; P < .01), glutathione (0.699 ± 0.032 vs 0.514 ± 0.056; P < .01), and catalase (32.13 ± 2.33 vs 27.19 ± 2.72; P < .01); and decreased malondialdehyde (1.027 ± 0.039 vs 1.462 ± 0.055; P < .01). CONCLUSIONS: Tetrandrine alleviated MCT-induced PAH through regulation of nitric oxide signaling pathway and antioxidant and antiproliferation effects.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Arterial/efeitos dos fármacos , Benzilisoquinolinas/farmacologia , Proteína Quinase Dependente de GMP Cíclico Tipo I/metabolismo , Hipertensão Pulmonar/prevenção & controle , Monocrotalina , Óxido Nítrico Sintase Tipo II/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Catalase/metabolismo , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Glutationa/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/enzimologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/enzimologia , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Masculino , Malondialdeído/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Artéria Pulmonar/enzimologia , Artéria Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fatores de Tempo , Remodelação Vascular/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
15.
Heart Vessels ; 30(3): 396-405, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24898407

RESUMO

Exposure to humid heat stress leads to the initiation of serious physiological dysfunction that may result in heat-related diseases, including heat stroke, heat cramp, heat exhaustion, and even death. Increasing evidences have shown that the humid heat stress-induced dysfunction of the cardiovascular system was accompanied with severe cardiomyocyte injury; however, the precise mechanism of heat stress-induced injury of cardiomyocyte remains unknown. In the present study, we hypothesized that humid heat stress promoted oxidative stress through the activation of angiotensin II (Ang II) in cardiomyocytes. To test our hypothesis, we established mouse models of humid heat stress. Using the animal models, we found that Ang II levels in serum were significantly up-regulated and that the Ang II receptor AT1 was increased in cardiomyocytes. The antioxidant ability in plasma and heart tissues which was detected by the ferric reducing/antioxidant power assay was also decreased with the increased ROS production under humid heat stress, as was the expression of antioxidant genes (SOD2, HO-1, GPx). Furthermore, we demonstrated that the Ang II receptor antagonist, valsartan, effectively relieved oxidative stress, blocked Ang II signaling pathway and suppressed cardiomyocyte apoptosis induced by humid heat stress. In addition, overexpression of antioxidant genes reversed cardiomyocyte apoptosis induced by Ang II. Overall, these results implied that humid heat stress increased oxidative stress and caused apoptosis of cardiomyocytes through the Ang II signaling pathway. Thus, targeting the Ang II signaling pathway may provide a promising approach for the prevention and treatment of cardiovascular diseases caused by humid heat stress.


Assuntos
Angiotensina II/metabolismo , Apoptose , Transtornos de Estresse por Calor/metabolismo , Temperatura Alta , Umidade , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Transdução de Sinais , Angiotensina II/sangue , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Células HEK293 , Transtornos de Estresse por Calor/tratamento farmacológico , Transtornos de Estresse por Calor/etiologia , Transtornos de Estresse por Calor/patologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Valsartana/farmacologia
16.
Chem Soc Rev ; 43(13): 4778-823, 2014 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-24733589

RESUMO

This review focuses on classifying different types of long wavelength absorbing BODIPY dyes based on the wide range of structural modification methods that have been adopted, and on tabulating their spectral and photophysical properties. The structure-property relationships are analyzed in depth with reference to molecular modeling calculations, so that the effectiveness of the different structural modification strategies for shifting the main BODIPY spectral bands to longer wavelengths can be readily compared, along with their effects on the fluorescence quantum yield (ΦF) values. This should facilitate the future rational design of red/NIR region BODIPY dyes for a wide range of different applications.


Assuntos
Compostos de Boro/síntese química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Compostos de Boro/química
18.
Angew Chem Int Ed Engl ; 53(36): 9544-9, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25045069

RESUMO

Simultaneous targeted cancer imaging, therapy and real-time therapeutic monitoring can prevent over- or undertreatment. This work describes the design of a multifunctional nanomicelle for recognition and precise near-infrared (NIR) cancer therapy. The nanomicelle encapsulates a new pH-activatable fluorescent probe and a robust NIR photosensitizer, R16FP, and is functionalized with a newly screened cancer-specific aptamer for targeting viable cancer cells. The fluorescent probe can light up the lysosomes for real-time imaging. Upon NIR irradiation, R16FP-mediated generation of reactive oxygen species causes lysosomal destruction and subsequently trigger lysosomal cell death. Meanwhile the fluorescent probe can reflect the cellular status and in situ visualize the treatment process. This protocol can provide molecular information for precise therapy and therapeutic monitoring.


Assuntos
Aptâmeros de Peptídeos/uso terapêutico , Raios Infravermelhos/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/radioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Aptâmeros de Peptídeos/síntese química , Compostos de Boro , Linhagem Celular Tumoral , Diagnóstico por Imagem , Corantes Fluorescentes , Humanos , Concentração de Íons de Hidrogênio , Lisossomos/patologia , Camundongos , Micelas , Monitorização Fisiológica , Nanopartículas , Espécies Reativas de Oxigênio/química
19.
Heliyon ; 10(6): e28243, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545193

RESUMO

Pancreatic cancer (PC) is a malignant digestive system tumor with a very poor prognosis. N6-methyladenosine (m6A) is mediated by a variety of readers and participates in important regulatory roles in PC. Based on TCGA_PAAD, ICGC_AU_PAAD, ICGC_CA_PAAD, GSE28735 and GSE62452 datasets, We mapped the multi-omics changes of m6A readers in PC and found that m6A readers, especially IGF2BP family genes, had specific changes and were significantly associated with poor prognosis. An unsupervised consensus clustering algorithm was used to explore the correlation between specific expression patterns of m6A readers in PC and enrichment pathways, tumor immunity and clinical molecular subtypes. Then, the principal component analysis (PCA) algorithm was used to quantify specific expression patterns and screen core genes. Machine learning algorithms such as Bootstrapping and RSF were used to quantify the expression patterns of core genes and construct a prognostic scoring model for PC patients. What's more, pharmacogenomic databases were used to screen sensitive drug targets and small molecule compounds for high-risk PC patients in an all-around and multi-angle way. Our study has not only provided new insights into personalized prognostication approaches, but also thrown light on integrating tailored risk stratification with precision therapy based on IGF2BP2-mediated m6A modification patterns.

20.
J Am Chem Soc ; 135(13): 5029-37, 2013 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-23464990

RESUMO

A general strategy for constructing high-effective upconversion nanocapsules based on triplet-triplet annihilation (TTA) was developed by loading both sensitizer and annihilator into BSA-dextran stabilized oil droplets. This strategy can maintain high translational mobility of the chromophores, avoid luminescence quenching of chromophore by aggregation, and decrease the O2-induced quenching of TTA-based upconversion emission. Pt(II)-tetraphenyl-tetrabenzoporphyrin (PtTPBP) and BODIPY dyes (BDP-G and BDP-Y with the maximal fluorescence emission at 528 and 546 nm, respectively) were chosen as sensitizer/annihilator couples to fabricate green and yellow upconversion luminescent emissive nanocapsules, named UCNC-G and UCNC-Y, respectively. In water under the atmospheric environment, interestingly, UCNC-G and UCNC-Y exhibit intense upconversion luminescence (UCL) emission (λex = 635 nm) with the quantum efficiencies (ΦUCL) of 1.7% and 4.8%, respectively, whereas very weak UCL emission (ΦUCL < 0.1%) was observed for the corresponding previous reported SiO2-coating nanosystems because of aggregation-induced fluorescence quenching of annihilators. Furthermore, application of theses upconversion nanocapsules for high-contrast UCL bioimaging in vivo of living mice without removing the skin was demonstrated under 635-nm excitation with low power density of 12.5 mW cm(-2).


Assuntos
Compostos de Boro/química , Nanocápsulas/química , Platina/química , Animais , Cápsulas/química , Interações Hidrofóbicas e Hidrofílicas , Substâncias Luminescentes/química , Camundongos , Microscopia Eletrônica de Transmissão , Imagem Molecular , Estrutura Molecular , Óleos/química , Dióxido de Silício/química , Solubilidade , Óleo de Soja/química , Água/química
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