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1.
Circ Res ; 132(11): e223-e242, 2023 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-37154056

RESUMEN

BACKGROUND: Doxorubicin is an effective chemotherapy drug for treating various types of cancer. However, lethal cardiotoxicity severely limits its clinical use. Recent evidence has indicated that aberrant activation of the cytosolic DNA-sensing cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING (stimulator of interferon genes) pathway plays a critical role in cardiovascular destruction. Here, we investigate the involvement of this mechanism in doxorubicin-induced cardiotoxicity (DIC). METHODS: Mice were treated with low-dose doxorubicin to induce chronic DIC. The role of the cGAS-STING pathway in DIC was evaluated in cGAS-deficiency (cGAS-/-), Sting-deficiency (Sting-/-), and interferon regulatory factor 3 (Irf3)-deficiency (Irf3-/-) mice. Endothelial cell (EC)-specific conditional Sting deficiency (Stingflox/flox/Cdh5-CreERT) mice were used to assess the importance of this pathway in ECs during DIC. We also examined the direct effects of the cGAS-STING pathway on nicotinamide adenine dinucleotide (NAD) homeostasis in vitro and in vivo. RESULTS: In the chronic DIC model, we observed significant activation of the cGAS-STING pathway in cardiac ECs. Global cGAS, Sting, and Irf3 deficiency all markedly ameliorated DIC. EC-specific Sting deficiency significantly prevented DIC and endothelial dysfunction. Mechanistically, doxorubicin activated the cardiac EC cGAS-STING pathway and its target, IRF3, which directly induced CD38 expression. In cardiac ECs, the cGAS-STING pathway caused a reduction in NAD levels and subsequent mitochondrial dysfunction via the intracellular NAD glycohydrolase (NADase) activity of CD38. Furthermore, the cardiac EC cGAS-STING pathway also regulates NAD homeostasis and mitochondrial bioenergetics in cardiomyocytes through the ecto-NADase activity of CD38. We also demonstrated that pharmacological inhibition of TANK-binding kinase 1 or CD38 effectively ameliorated DIC without compromising the anticancer effects of doxorubicin. CONCLUSIONS: Our findings indicate a critical role of the cardiac EC cGAS-STING pathway in DIC. The cGAS-STING pathway may represent a novel therapeutic target for preventing DIC.


Asunto(s)
Cardiotoxicidad , Transducción de Señal , Ratones , Animales , NAD/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Doxorrubicina/toxicidad
2.
J Nucl Cardiol ; 30(5): 2058-2067, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37095328

RESUMEN

BACKGROUND: The aim of this study was to investigate the feasibility and diagnostic value of myocardial flow reserve (MFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) in the functional evaluation of myocardial bridge (MB). METHODS: From May 2017 to July 2021, patients with angiographically confirmed isolated MB on the left anterior descending artery (LAD) who underwent dynamic SPECT myocardial perfusion imaging were retrospectively included. The assessment of semiquantitative indices of myocardial perfusion (summed stress scores, SSS) and quantitative parameters (MFR) was performed. RESULTS: A total of 49 patients were enrolled. The mean age of the subjects was 61.0 ± 9.0 years. All of the patients were symptomatic, and 16 cases (32.7%) presented with typical angina. SPECT-derived MFR showed a borderline significantly negative correlation with SSS (r = 0.261, P = .070). There was a trend of higher prevalence of impaired myocardial perfusion defined as MFR < 2 than as SSS ≥ 4 (42.9% vs 26.5%; P = .090). CONCLUSION: Our data support that SPECT MFR may be a useful parameter for the functional assessment of MB. In patients with MB, the use of dynamic SPECT could be a potential method for hemodynamic assessment.


Asunto(s)
Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Puente Miocárdico , Imagen de Perfusión Miocárdica , Humanos , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Perfusión , Imagen de Perfusión Miocárdica/métodos , Circulación Coronaria
3.
Opt Express ; 30(19): 34129-34139, 2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-36242433

RESUMEN

The infrared absorption efficiency is essential for an infrared sensor. We propose a quartz bulk acoustic wave (BAW) uncooled infrared sensor coated with MXene quantum dot film. The infrared detection is realized by measuring the resonant frequency of a Y-cut quartz BAW sensitive unit. An infrared sensor is fabricated by MEMS process, then the MXene quantum dot film is coated through the spin coating technology. The mechanism of infrared absorption enhancement is analyzed. Test results show that after coating the film, the responsivity (R) of the sensor increased by nearly 41% at a wavelength of 830nm, from 10.88MHz/W to 15.28 MHz/W. The quartz BAW infrared sensor combined with MXene quantum dots film has the potential of high-performance infrared detection.

4.
J Am Chem Soc ; 138(7): 2118-21, 2016 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-26840838

RESUMEN

Making dynamic three-dimensional (3D) structures capable of reversible shape changes or locomotion purely out of dry polymers is very difficult. Meanwhile, no previous dynamic 3D structures can be remade into new configurations while being resilient to mechanical damages and low temperature. Here, we show that light-activated transesterification in carbon nanotube dispersed liquid crystalline vitrimers enables flexible design and easy building of dynamic 3D structures out of flat films upon irradiation of light without screws, glues, or molds. Shining light also enables dynamic 3D structures to be quickly modified on demand, restored from distortion, repaired if broken, in situ healed when microcrack appears, assembled for more sophisticated structures, reconfigured, and recycled after use. Furthermore, the fabrication, reconfiguration, actuation, reparation, and assembly as well as healing can be performed even at extremely low temperatures (e.g., -130 °C).

5.
Nat Mater ; 13(1): 36-41, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24292422

RESUMEN

Liquid-crystal elastomers (LCEs) are a class of actively moving polymers with remarkable practical potential for converting external stimuli into mechanical actuation. However, real-world applications of LCEs are lacking because macroscopic orientation of liquid-crystal order, which is required for reversible actuations, is hard to achieve in practice. Here we show that the processing bottleneck of LCEs can be overcome by introducing exchangeable links in place of permanent network crosslinks, a concept previously demonstrated for vitrimers. Liquid-crystal elastomers with exchangeable links (xLCEs) are mouldable, allow for easy processing and alignment, and can be subsequently altered through remoulding with different stress patterns, thus opening the way to practical xLCE actuators and artificial muscles. Surprisingly, instead of external-stress relaxation through the creep of non-liquid-crystal transient networks with exchangeable links, xLCEs develop strong liquid-crystal alignment as an alternative mechanism of mechanical relaxation.

6.
Front Med ; 18(3): 465-483, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38644399

RESUMEN

Atherosclerosis is a chronic artery disease that causes various types of cardiovascular dysfunction. Vascular smooth muscle cells (VSMCs), the main components of atherosclerotic plaque, switch from contractile to synthetic phenotypes during atherogenesis. Ubiquitylation is crucial in regulating VSMC phenotypes in atherosclerosis, and it can be reversely regulated by deubiquitinases. However, the specific effects of deubiquitinases on atherosclerosis have not been thoroughly elucidated. In this study, RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases, which revealed that silencing OTUB1 inhibited PDGF-BB-stimulated VSMC phenotype switch. Further in vivo studies using Apoe-/- mice revealed that knockdown of OTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque phenotype. Moreover, VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencing OTUB1 in vitro. Unbiased RNA-sequencing data indicated that knocking down OTUB1 influenced VSMC differentiation, adhesion, and proliferation. Mass spectrometry of ubiquitinated protein confirmed that proteins related to cell growth and migration were differentially ubiquitylated. Mechanistically, we found that OTUB1 recognized the K707 residue ubiquitylation of PDGFRß with its catalytic triad, thereby reducing the K48-linked ubiquitylation of PDGFRß. Inhibiting OTUB1 in VSMCs could promote PDGFRß degradation via the ubiquitin-proteasome pathway, so it was beneficial in preventing VSMCs' phenotype switch. These findings revealed that knocking down OTUB1 ameliorated VSMCs' phenotype switch and atherosclerosis progression, indicating that OTUB1 could be a valuable translational therapeutic target in the future.


Asunto(s)
Aterosclerosis , Proliferación Celular , Músculo Liso Vascular , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Ubiquitinación , Animales , Humanos , Masculino , Ratones , Aterosclerosis/metabolismo , Aterosclerosis/genética , Becaplermina/farmacología , Movimiento Celular , Células Cultivadas , Cisteína Endopeptidasas/metabolismo , Cisteína Endopeptidasas/genética , Enzimas Desubicuitinizantes/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo
7.
Signal Transduct Target Ther ; 9(1): 45, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374140

RESUMEN

Cardiac fibroblasts (CFs) are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure (HF). TEAD1 has been shown to be essential for heart development and homeostasis. However, fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood. Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction (TAC) and Ang-II infusion. Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs- and myofibroblasts-specific Cre mice. Echocardiographic and histological analyses demonstrated that CFs- and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor, VT103, ameliorated TAC-induced cardiac remodeling. Mechanistically, RNA-seq and ChIP-seq analysis identified Wnt4 as a novel TEAD1 target. TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway, and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression. Furthermore, co-immunoprecipitation combined with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4, leading to the binding and activation of the Wnt4 promoter. In conclusion, TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signalling pathway.


Asunto(s)
Factores de Transcripción de Dominio TEA , Factores de Transcripción , Remodelación Ventricular , Animales , Ratones , Miofibroblastos/metabolismo , Miofibroblastos/patología , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factores de Transcripción de Dominio TEA/genética , Factores de Transcripción de Dominio TEA/metabolismo , Factores de Transcripción/genética , Remodelación Ventricular/genética , Proteína Wnt4/metabolismo , Fibroblastos/metabolismo , Proteínas que Contienen Bromodominio/metabolismo
8.
Chin Med J (Engl) ; 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38445387

RESUMEN

BACKGROUND: Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury. METHODS: This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (5 and 42 days post-MI) and a series of biomarkers/histological studies were performed. RESULTS: The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH. CONCLUSIONS: The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

9.
Int J Biol Sci ; 19(12): 3661-3677, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37564202

RESUMEN

Heart failure is the leading cardiovascular comorbidity in chronic kidney disease (CKD) patients. Among the types of heart failure according to ejection fraction, heart failure with preserved ejection fraction (HFpEF) is the most common type of heart failure in CKD patients. However, the specific animal model of HFpEF afer CKD is currently missing. In this study, we determined the heart failure characteristics and dynamic progression in CKD mice. Based on these features, we established the practical HFpEF after CKD mouse model using 5/6 subtotal nephrectomy and retinol administration. Active apoptosis, impaired calcium handling, an imbalance between eNOS and oxidative stress and engaged endoplasmic reticulum stress were observed in our model. RNSseq revealed distinct gene expression patterns between HFpEF after CKD and metabolic induced-HFpEF. Furthermore, we revealed the potential mechanism of the pro-HFpEF effect of retinol. Serum accumulation of retinol in CKD prompts myocardial hypertrophy and fibrosis by activating JAK2 and phosphorylating STAT5. Finally, using small molecule inhibitor AC-4-130, we found STAT5 phosphorylation inhibitor may be a potential intervention target for HFpEF after CKD. In conclusion, we provide a novel animal model and a potential drug target for HFpEF intervention in CKD.


Asunto(s)
Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Ratones , Animales , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Vitamina A/uso terapéutico , Vitamina A/metabolismo , Quinasas Janus/metabolismo , Factor de Transcripción STAT5/metabolismo , Volumen Sistólico , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Modelos Animales de Enfermedad , Insuficiencia Renal Crónica/tratamiento farmacológico
10.
Quant Imaging Med Surg ; 13(9): 6215-6227, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37711819

RESUMEN

Background: Angio-based index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) have been developed, however, the differences between baseline and hyperemic data and their effects on their computation have not yet been discussed. This study aimed to compare the diagnostic performance of a novel method for calculating IMR and FFR from coronary angiography under baseline and hyperemic conditions. Methods: We performed a retrospective study to investigate the diagnostic performance of angiography-derived IMR (AccuIMR) and FFR (AccuFFRangio) computed from the hyperemic condition (AccuIMRhyp, AccuFFRangiohyp) and baseline condition (AccuIMRbase, AccuFFRangiobase) in 101 consecutive patients with chronic coronary syndrome (CCS) who underwent measurements of IMR and FFR at a single center, using wire-based IMR and FFR as the reference standard. Results: AccuIMRhyp showed much better correlation with IMR than AccuIMRbase (r=0.77 vs. 0.47, P<0.001). The diagnostic accuracy and area under the curve (AUC) for identifying significant microvascular dysfunction was higher for AccuIMRhyp than AccuIMRbase [92.1% (95% CI: 85.0-96.5%) vs. 83.2% (95% CI: 74.4-89.9%), P=0.012; 0.942 (95% CI: 0.877-0.979) vs. 0.815 (95% CI: 0.726-0.886), P=0.003]. The computed AccuFFRangio showed good correlations with FFR and good diagnostic performance under both hyperemic and baseline conditions [r=0.68 vs. 0.68, P>0.99; diagnostic accuracy =95.9% (95% CI: 89.8-98.9%) vs. 94.9% (95% CI: 88.4-98.3%), P=0.728; AUC =0.989 (95% CI: 0.942-1.000) vs. 0.973 (95% CI: 0.919-0.995), P=0.381]. The net reclassification index (NRI) demonstrated that hyperemic group had improved reclassification ability compared to the baseline group in identification of IMR >25 (NRI =0.20, P<0.001) and FFR ≤0.8 (NRI =0.11, P<0.001). Conclusions: By comparing the calculated angio-derived IMR and FFR under the baseline and hyperemic conditions, this study demonstrates that AccuIMR calculation is more accurate using the hyperemic condition, while AccuFFRangio calculation is accurate under both conditions.

11.
Adv Sci (Weinh) ; 10(21): e2206801, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37310417

RESUMEN

Microvascular endothelial cells (MiVECs) impair angiogenic potential, leading to microvascular rarefaction, which is a characteristic feature of chronic pressure overload-induced cardiac dysfunction. Semaphorin3A (Sema3A) is a secreted protein upregulated in MiVECs following angiotensin II (Ang II) activation and pressure overload stimuli. However, its role and mechanism in microvascular rarefaction remain elusive. The function and mechanism of action of Sema3A in pressure overload-induced microvascular rarefaction, is explored, through an Ang II-induced animal model of pressure overload. RNA sequencing, immunoblotting analysis, enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and immunofluorescence staining results indicate that Sema3A is predominantly expressed and significantly upregulated in MiVECs under pressure overload. Immunoelectron microscopy and nano-flow cytometry analyses indicate small extracellular vesicles (sEVs), with surface-attached Sema3A, to be a novel tool for efficient release and delivery of Sema3A from the MiVECs to extracellular microenvironment. To investigate pressure overload-mediated cardiac microvascular rarefaction and cardiac fibrosis in vivo, endothelial-specific Sema3A knockdown mice are established. Mechanistically, serum response factor (transcription factor) promotes the production of Sema3A; Sema3A-positive sEVs compete with vascular endothelial growth factor A to bind to neuropilin-1. Therefore, MiVECs lose their ability to respond to angiogenesis. In conclusion, Sema3A is a key pathogenic mediator that impairs the angiogenic potential of MiVECs, which leads to cardiac microvascular rarefaction in pressure overload-induced heart disease.


Asunto(s)
Cardiopatías , Rarefacción Microvascular , Animales , Ratones , Células Endoteliales/metabolismo , Semaforina-3A/genética , Semaforina-3A/metabolismo , Factor A de Crecimiento Endotelial Vascular
12.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(11): 914-9, 2012 Nov.
Artículo en Zh | MEDLINE | ID: mdl-23363671

RESUMEN

OBJECTIVE: To determine whether circulating level of catestatin (CST) could provide prognostic information independently of conventional risk markers for the development of in-hospital heart failure in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: The data of 120 STEMI patients (mean age: 61 years, 73% male) were collected from the Second Hospital of Shanxi Medical University and Taiyuan Central Hospital between November 2010 and September 2011.The patients were categorized into 4 groups according to CST (ng/L) quartile: ≤ 74.72, 74.73-79.67, 79.68 - 84.21 and ≥ 84.22 ng/L. Clinical features, therapeutic approaches were compared among groups. The patients were also grouped according to Killip class: Killip level I (n = 68), Killip level II (n = 23), Killip level III (n = 18), Killip level IV (n = 11). CST, NE and NT-proBNP were compared among groups. The Spearma rank correlation and multivariate logistic regression analysis were applied to determine the association between risk factors and in-hospital heart failure. Receiver-operator characteristic (ROC) curve was performed to evaluate the power of CST and NT-proBNP on predicting in-hospital heart failure. RESULTS: Gender, hospital days, past history of smoking, hypertension, myocardial infarction, CK-MB peak level, TnI peak level, heart rate, blood pressure, blood glucose, blood lipid levels on admission and early reperfusion therapy were similar among groups. Patients with higher CST values were more likely to be older, to have lower body mass index, to have higher white blood cell count, CysC, hs-CRP, NE, NT-proBNP, past history of angina, diabetes mellitus, being diuretic users, and to have a lower ejection fraction (all P < 0.05). Higher CST levels were also associated with increased risk of heart failure (P < 0.05). In proportion with the deterioration of the cardiac function, CST, NE, NT-proBNP concentration gradually increased (all P < 0.05). Spearman rank correlation analysis showed that the CST was negatively correlated with LVEF (r(s) = -0.923, P < 0.001) and positively correlated with NT-proBNP (r(s) = 0.884, P < 0.001). After multivariate adjustment, CST remained to be an independent risk factor for the development of in-hospital heart failure (OR = 1.125, 95%CI: 1.056 - 1.198;P < 0.001). The area under the ROC curve of CST and NT-proBNP was 0.777 and 0.874. Using CST = 77.29 ng/L as a cut-off value, the sensitivity was 92.8% and specificity was 70.6% for predicting the development of in-hospital heart failure. CONCLUSION: The plasma CST level is an independent predictor for the development of in-hospital heart failure in patients with STEMI.


Asunto(s)
Catecoles/farmacología , Cromogranina A/sangre , Insuficiencia Cardíaca/etiología , Infarto del Miocardio/complicaciones , Fragmentos de Péptidos/sangre , Anciano , Catecoles/antagonistas & inhibidores , Femenino , Insuficiencia Cardíaca/diagnóstico , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Pronóstico , Estudios Prospectivos , Factores de Riesgo
13.
Front Psychol ; 13: 1111028, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36726501

RESUMEN

During the COVID-19 pandemic, online learning has become one of the important ways of higher education because it is not confined by time and place. How to ensure the effectiveness of online learning has become the focus of education research, and the role of the "online learning community" cannot be ignored. In the context of the Internet of Things (IoT), we try to build up a new online learning community model: (1) First, we introduce the Kolb learning style theory to identify different online learning styles; (2) Second, we use a clustering algorithm to identify the nature of different learning style groups; and (3) Third, we introduce the group dynamics theory to design the dimensions of the questionnaire and combine the Analytic Hierarchy Process (AHP) method to identify the key influencing factors of the online learning community. We take business administration majors and students in universities as an example. The results show that (1) as a machine learning method, the clustering algorithm method is superior to the random construction method in identifying different learning style groups, and (2) our method can well judge the importance of each factor based on hierarchical analysis and clarify the different roles of factors in the process of knowledge transfer. This study can provide a useful reference for the sustainable development of online learning in higher education.

14.
Membranes (Basel) ; 12(10)2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36295714

RESUMEN

Forward osmosis (FO) is a promising separation technology to overcome the challenges of pressure-driven membrane processes. The FO process has demonstrated profound advantages in treating feeds with high salinity and viscosity in applications such as brine treatment and food processing. This review discusses the advancement of FO membranes and the key membrane properties that are important in real applications. The membrane substrates have been the focus of the majority of FO membrane studies to reduce internal concentration polarization. However, the separation layer is critical in selecting the suitable FO membranes as the feed solute rejection and draw solute back diffusion are important considerations in designing large-scale FO processes. In this review, emphasis is placed on developing FO membrane selective layers with a high selectivity. The effects of porous FO substrates in synthesizing high-performance polyamide selective layer and strategies to overcome the substrate constraints are discussed. The role of interlayer in selective layer synthesis and the benefits of nanomaterial incorporation will also be reviewed.

15.
Drug Dev Ind Pharm ; 37(1): 33-40, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20545503

RESUMEN

OBJECTIVE: To reduce the frequency of administration and improve patient compliance, novel levofloxacin sustained-release capsules with suitable in vitro release profiles and good bioavailability were developed. MATERIALS AND METHODS: A fluidized bed was used to prepare levofloxacin pellets by spraying the drug solution onto blank pellets. Then the pellets were coated with either Surelease water dispersion or Eudragit® NE30D water dispersion to achieve sustained-release characteristics. The mixed pellets containing 15% of the uncoated pellets and 85% of the coated pellets were filled into the hard gelatin capsules. In vitro release test was performed with the capsules. A single-dose pharmacokinetic study of the capsules was carried out in beagle dogs. RESULTS: Although Eudragit® NE30D-coated pellets and Surelease-coated pellets showed similar sustained-release profiles in vitro, their in vivo pharmacokinetic characteristics exhibited significant difference. Unsuccessful in vivo-in vitro correlation was shown in Eudragit® NE30D-coated pellets with a relative bioavailability of only 41.5%, whereas Surelease-coated pellets achieved best sustained-release feature both in vitro and in vivo with a relative bioavailability of 103.0%. CONCLUSION: Statistical analysis indicated that the capsules containing Surelease-coated pellets had a satisfactory sustained-release behavior and a desired pharmacokinetic property.


Asunto(s)
Levofloxacino , Ofloxacino/química , Ofloxacino/farmacocinética , Animales , Disponibilidad Biológica , Cápsulas/química , Celulosa/administración & dosificación , Celulosa/análogos & derivados , Celulosa/química , Celulosa/farmacocinética , Química Farmacéutica , Preparaciones de Acción Retardada , Perros , Esquema de Medicación , Implantes de Medicamentos/química , Excipientes/química , Masculino , Ofloxacino/administración & dosificación , Solubilidad , Tecnología Farmacéutica
16.
Front Cell Dev Biol ; 9: 642080, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34136476

RESUMEN

Post-transcriptional modifications play pivotal roles in various pathological processes and ischemic disorders. However, the role of N7-methylguanosine (m7G), particularly m7G in mRNA, on post-ischemic angiogenesis remains largely unknown. Here, we identified that methyltransferase like 1 (METTL1) was a critical candidate responsible for a global decrease of m7G within mRNA from the ischemic tissues. The in vivo gene transfer of METTL1 improved blood flow recovery and increased angiogenesis with enhanced mRNA m7G upon post-ischemic injury. Increased METTL1 expression using plasmid transfection in vitro promoted HUVECs proliferation, migration, and tube formation with a global increase of m7G in mRNA. Mechanistically, METTL1 promoted VEGFA mRNA translation in an m7G methylation-dependent manner. Our findings emphasize a critical link between mRNA m7G and ischemia and provide a novel insight of targeting METTL1 in the therapeutic angiogenesis for ischemic disorders, including peripheral arterial disease.

17.
Front Cardiovasc Med ; 8: 746934, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34660745

RESUMEN

Objective: Previous studies have demonstrated the protective effects of renal denervation (RDN) in pre-existing heart failure, but the effects of immediate RDN after acute myocardial infarction (AMI) on subsequent cardiac remodeling have not been reported. This study aimed to investigate the cardioprotective effects of immediate RDN after AMI and its underlying mechanism. Methods: AMI was induced by intracoronary gelatin sponge embolization in 14 Shanghai white pigs that were randomized to undergo either renal angiography (AMI+sham group) or RDN (AMI+RDN group) after 1 h of hemodynamic monitoring. Cardiac function of the two groups was measured at baseline, 1 h post-AMI and at the 1 month follow-up (1M-FU) by transthoracic echocardiography (TTE). Plasma NT-proBNP, soluble ST2 (sST2), norepinephrine (NE), and renin-angiotensin-aldosterone system activity were detected simultaneously. The renal cortex was harvested for NE measurement after the 1M-FU, and the renal arteries were stained with tyrosine hydroxylase for the evaluation of sympathetic activity. Heart tissues in the non-ischemic areas were collected to assess histological and molecular left ventricular (LV) remodeling by pathological staining, RT-PCR, and western blotting. Results: There was no difference in the hemodynamic stability or cardiac function between the two groups at baseline and 1 h post-AMI. Six pigs from each of the two groups completed the 1M-FU. TTE analysis revealed the improved cardiac function of immediate RDN in the AMI+RDN group and circulating NT-proBNP levels were lower than those in the AMI+sham group. Further analysis showed significantly less interstitial fibrosis in the remote non-ischemic myocardium after immediate RDN, together with decreased cardiomyocyte hypertrophy and inflammatory cell infiltration. sST2 levels in circulating and myocardial tissues of animals in the AMI+RDN group were significantly higher than those in the AMI+sham group, accompanied by corresponding alterations in IL-33/ST2 and downstream signaling. Conclusions: Immediate RDN can improve cardiac function and myocardial remodeling after AMI via modulation of IL-33/ST2 and downstream signaling.

18.
Chem Sci ; 9(5): 1392, 2018 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-30090314

RESUMEN

[This corrects the article DOI: 10.1039/C7SC02967E.].

19.
Chem Sci ; 9(3): 623-628, 2018 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-29629127

RESUMEN

Efficient and cost-effective solar steam generation requires self-floating evaporators which can convert light into heat, prevent unnecessary heat loss and greatly accelerate evaporation without solar concentrators. Currently, the most efficient evaporators (efficiency of ∼80% under 1 sun) are invariably built from inorganic materials, which are difficult to mold into monolithic sheets. Here, we present a new polymer which can be easily solution processed into a self-floating monolithic foam. The single-component foam can be used as an evaporator with an efficiency at 1 sun comparable to that of the best graphene-based evaporators. Even at 0.5 sun, the efficiency can reach 80%. Moreover, the foam is mechanically strong, thermally stable to 300 °C and chemically resistant to organic solvents.

20.
Chem Sci ; 8(1): 724-733, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-28616137

RESUMEN

Smart polymers have been playing indispensable roles in our lives. However, it is challenging to combine more than three stimuli-responses or functionalities into one polymer, not to mention integrating multi-stimuli responsivity and multi-functionality at the same time. Vitrimers, an emerging type of materials, are covalently crosslinked networks that can be reprocessed but are still infusible and insoluble. Herein, we show that simply introducing oligoaniline into a vitrimer results in a covalently crosslinked material that can respond to six different stimuli (heat, light, pH, voltage, metal ions and redox chemicals) and perform six functions (shape memory, welding, healing, recycling, electro-chromism and adsorption of metal ions). New properties, which cannot be found in either neat vitrimers or oligoanilines, are generated, including photo-heal-ability, photo-weldability, pH-induced shape memory, enhancement of the photo-thermal effect due to metal ions absorption and simultaneous multi-tasking operations. Furthermore, the material is low-cost and suitable for large-scale mass production.

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