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1.
Small ; 20(10): e2306211, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37875779

RESUMO

The stability of aqueous Zn-ion batteries (AZIBs) is detrimentally influenced by the formation of Zn dendrites and the occurrence of parasitic side reactions at the Zn metal anode (ZMA)-electrolyte interface. The strategic manipulation of the preferential crystal orientation during Zn2+ plating serves as an essential approach to mitigate this issue. Here, Zn aspartate (Zn-Asp), an electrolyte additive for AZIBs, is introduced not only to optimize the solvation structure of Zn2+ , but also to crucially promote preferential Zn2+ plating on the (002) crystal plane of ZMA. As a result, both side reactions and Zn dendrites are effectively inhibited, ensuring an anode surface free of both dendrites and by-products. The implementation of Zn-Asp leads to significant enhancements in both Zn||Zn symmetric and Zn||Ti batteries, which demonstrate robust cyclability of over 3200 h and high Coulombic efficiency of 99.29%, respectively. Additionally, the Zn||NaV3 O8 ·1.5H2 O full battery exhibits remarkable rate capability, realizing a high capacity of 240.77 mA h g-1 at 5 A g-1 , and retains 92.7% of its initial capacity after 1000 cycles. This research underscores the vital role of electrolyte additives in regulating the preferential crystal orientation of ZMA, thereby contributing to the development of high-performing AZIBs.

2.
Urol Int ; 108(2): 118-127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38185112

RESUMO

INTRODUCTION: Overactive bladder symptoms (OABSs) affect patients' quality of life (QOL) worldwide. This pooled analysis compared the efficacy and safety of mirabegron add-on tamsulosin with those of tamsulosin add-on placebo in OABS treatment. METHODS: PubMed, Embase, MEDLINE, and the Cochrane Controlled Trial Register databases were searched for randomized controlled trials (RCTs) examining the efficacy of mirabegron add-on therapy to tamsulosin in the treatment of OABS. Moreover, references from the selected studies were screened. Review Manager 5.4 was used to analyze data. RESULTS: Four RCTs involving 1,397 patients with OABS were selected. Of the total, 697 patients receiving mirabegron add-on tamsulosin constituted the experimental group, and 700 patients receiving tamsulosin add-on placebo constituted the control group. The efficacy endpoints were as follows: mean number of micturition per day (mean difference [MD] = -0.26, 95% confidence interval [CI] = -0.41 to -0.10, p = 0.0001), urgency episodes per day (MD = -0.67, 95% CI = -1.02 to -0.32, p = 0.0002), urgency urinary incontinence (UUI) episodes per day (MD = -0.42, 95% CI = -0.66 to -0.19, p = 0.0005), mean volume voided/micturition (MD = 10.84, 95% CI = 4.97-16.71, p = 0.0003), total International Prostate Symptom Score (IPSS) (MD = -2.01, 95% CI = -4.02 to -0.01, p = 0.05), and IPSS QOL index (MD = -0.65, 95% CI = -0.94 to -0.35, p < 0.0001). Mirabegron therapy, an add-on therapy to tamsulosin, was effective in treating patients with OABS. Moreover, mirabegron might reduce the total IPSS (MD = -2.01, 95% CI = -4.02 to -0.01, p = 0.05). The safety endpoint, treatment-emergent adverse events (odds ratio = 0.94, 95% CI = 0.78-1.13, p = 0.49), suggested that although mirabegron was well-tolerated, it possibly increased the post-void residual urine volume (MD = 10.28, 95% CI = 1.82-18.75, p = 0.02). CONCLUSION: Combination therapy using mirabegron and tamsulosin may be effective in treating patients with non-neurogenic OABS in terms of UUI episodes, total IPSS, and IPSS QOL index. However, its effectiveness must be verified by analyzing additional factors for OABS through further RCTs.


Assuntos
Tiazóis , Bexiga Urinária Hiperativa , Incontinência Urinária , Masculino , Humanos , Tansulosina/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/diagnóstico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Acetanilidas , Método Duplo-Cego
3.
J Clin Rheumatol ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38389131

RESUMO

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection in immunocompromised children with systemic lupus erythematosus (SLE). Prophylaxis against PJP in high-risk children is crucial, but the risk factors for PJP in children with SLE are not adequately characterized. This study sought to identify the risk factors for PJP in long-term glucocorticoid-treated pediatric SLE patients. METHODS: This study encompassed 71 treatment episodes involving 64 children with prolonged (≥4 weeks) high-dose (≥20 mg/d prednisone) steroid regimens. Fourteen treatment episodes involved the PJP, whereas others did not. Risk factors for PJP were assessed through Cox regression. The predictive value of these factors was evaluated using receiver operating characteristic curves. The incidence of PJP in different risk groups was compared using the Kaplan-Meier method. RESULTS: The creatinine (hazard ratio, 1.009; 95% confidence interval [CI], 1.001-1.017; p = 0.021) and the lowest lymphocyte count (hazard ratio, 0.007; 95% CI, 0.000-0.373; p = 0.014) were independent risk factors for PJP in children with SLE. The receiver operating characteristic curve showed that using creatinine greater than 72.5 µmol/L and the lowest lymphocyte count less than 0.6 × 109/L as risk predictors for PJP resulted in an area under the curve value of 0.934 (95% CI, 0.870-0.997; p < 0.001). The study revealed a significant increase in PJP prevalence (p < 0.001) in children with elevated creatinine levels and low lymphocyte count. CONCLUSIONS: Elevated levels of creatinine and decreased lymphocyte count are identified as distinct risk factors for PJP in children with SLE who receive prolonged high-dose steroid therapy.

4.
Angew Chem Int Ed Engl ; 63(29): e202405357, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38682802

RESUMO

The rapid growth of flexible quasi-solid-state thermocells (TECs) provides a fresh way forward for wearable electronics. However, their insufficient mechanical strength and power output still hinder their further applications. This work demonstrates a one-stone-two-birds strategy to synergistically enhance the mechanical and thermoelectrochemical properties of the [Fe(CN)6]3-/4--based TECs. By introducing Hofmeister effect and multiple non-covalent interactions via betaine zwitterions, the mechanical strength of the conventional brittle gelatin hydrogel electrolytes is substantially improved from 50 to 440 kPa, with a high stretchability approaching 250 %. Meanwhile, the betaine zwitterions strongly affect the solvation structure of [Fe(CN)6]3- ions, thus enlarging the entropy difference and raising the thermoelectrochemical Seebeck coefficient from 1.47 to 2.2 mV K-1. The resultant quasi-solid-state TECs exhibit a normalized output power density of 0.48 mW m-2 K-2, showing a notable improvement in overall performance compared to their counterparts without zwitterion regulation. The intrinsic thermo-reversible property also allows the TECs to repeatedly self-recover through sol-gel transformations, ensuring reliable energy output and even recycling of TECs in case of extreme mechanical damages. An energy-autonomous smart glove consisting of eighteen individual TECs is further designed, which can simultaneously monitor the temperature of different positions on any touched object, demonstrating high potential in wearable applications.

5.
J Gene Med ; 25(11): e3549, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37271571

RESUMO

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a prevalent type of urological malignancy. The present study aimed to predict biomarkers for KIRC. METHODS: We collected transcriptomic and clinical information for KIRC from The Cancer Genome Atlas and GSE22541 cohorts. RESULTS: Unsupervised clustering of 35 epithelial-mesenchymal transformation (EMT)-related differentially expressed gene profiles divided samples into two clusters with distinct immune characteristics. Six genes (IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN) were found to construct a prognostic risk model using multivariate Cox regression analysis. Kaplan-Meier analysis suggested the better prognosis of the KIRC patients in the low-risk group than that in the high-risk group. Immune infiltration analyses was conducted using xCell and single-sample gene set enrichment analysis, indicating that the risk score was associated with the immune microenvironment of the KIRC. Prognostic marker gene-targeted medications with high drug sensitivity were predicted in KIRC patients. CONCLUSIONS: In summary, the present study identified IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN as prognostic biomarkers, providing insight into immunotherapy and gene-targeted drugs of KIRC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Prognóstico , Transição Epitelial-Mesenquimal/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Biomarcadores , Rim , Microambiente Tumoral
6.
Small ; 18(12): e2104922, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34921579

RESUMO

The enormous demand for waste heat utilization and burgeoning eco-friendly wearable materials has triggered huge interest in the development of thermoelectric materials that can harvest low-cost energy resources by converting waste heat to electricity efficiently. In particular, due to their high flexibility, nontoxicity, cost-effectivity, and promising applicability in various fields, organic thermoelectric materials are drawing more attention compared with their toxic, expensive, heavy, and brittle inorganic counterparts. Organic thermoelectric materials are approaching the figure of merit of the inorganic ones via the construction and optimization of unique transport pathways and device geometries. This review presents the recent development of the interdependence and decoupling principles of the thermoelectric efficiency parameters as well as the new achievements of high performance organic thermoelectric materials. Moreover, this review also discusses the advances in the thermoelectric devices with emphasis on their energy-related applications. It is believed that organic thermoelectric materials are emerging as green energy alternatives rivaling their conventional inorganic counterparts in the efficient and pure electricity harvesting from waste heat and solar thermal energy.


Assuntos
Eletricidade , Temperatura Alta
7.
Cryobiology ; 108: 57-66, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35918000

RESUMO

Cartilage transplantation is an effective way to repair, reconstruct, and replace damaged articular cartilage (AC) but its use is limited by the inability to preserve AC for long periods of time. Vitrification is an ideal choice for long-term storage of AC, and multiple cryoprotective agents (CPAs) with high concentration are usually used. To obtain high cell viability, chondrocytes at all locations inside AC should be protected properly by the CPAs during cooling and rewarming. Hence, it is important to know the mass transport properties of multiple CPAs as they synergistically infiltrate AC. In this study, a mathematical model to describe the mass transport behavior of multiple CPAs in AC was developed based on the mixture-averaged diffusion model. In addition, a methodology for the simultaneous determination of dimethyl sulfoxide, glycerol, ethylene glycol, and propylene glycol by carbon-13 nuclear magnetic resonance was established. The model is applicable for predicting single- and multiple-CPA permeation into AC, and its accuracy was verified by a massive experimental dataset. Simulation results showed reverse diffusion in the multiple-CPA permeation process, which was not found in the single-CPA permeation process. This curious phenomenon shows the sharp contrast between the diffusion behavior of a binary mixture and a multicomponent mixture.


Assuntos
Cartilagem Articular , Crioprotetores , Criopreservação/métodos , Crioprotetores/farmacologia , Dimetil Sulfóxido , Etilenoglicol , Glicerol/farmacologia , Propilenoglicol , Vitrificação
8.
Small ; 17(38): e2100505, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34047067

RESUMO

Thermoelectrics that enable direct heat-electricity conversion possess unique advantages for green and renewable energy revolution and have received rapidly growing attention in the past decade. Among various thermoelectric materials, metal-organic frameworks (MOFs) with intrinsic high porosity and tunable physical/chemical properties are emerging as a promising class of materials that have been demonstrated to exhibit many unique merits for thermoelectric applications. Their structural topologies and thermoelectric properties can be facilely regulated by precisely selecting and arranging metal centers and organic ligands. Besides, a large variety of guest molecules can be incorporated within their pores, giving rise to novel avenues of raising energy-conversion efficiency. This review focuses on the recent advances in designing conductive MOFs and MOF-based composites for thermoelectric applications. It first introduces the fundamental thermoelectric parameters and the underlying regulation mechanisms specifically effective for MOFs, then summarizes the related studies conducted in recent years, where the structural design strategies of tuning thermoelectric properties are demonstrated and discussed. In the final part, conclusions and perspectives with the envision of an outlook for this promising area are presented.

9.
Protein Expr Purif ; 187: 105942, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34284069

RESUMO

Telomerase, which is overexpressed in approximately 90% of liver cancer cells, is an ideal target for anti-liver cancer therapy. LPTS, a putative liver tumor suppressor, is the only human-derived protein that can bind telomerase directly and inhibit the extension of telomere activity. Our previous studies demonstrated that TAT-LPTS-LC (TLC), a recombinant protein fused by the C-terminal 133-328 fragment of LPTS and TAT peptides, could be delivered into cells to inhibit telomerase-positive hepatoma cell growth in vitro and in vivo with very low toxicity. In the present study, E. coli strains which expressed TLC in abundance were screened and cultured in a laboratory bioreactor. A reproducible protein separation process was built, and this process was suitable for industrial amplification. The yields of TLC protein were up to 184 mg in one batch with a purity of approximately 95%. The purified TLC protein had a similar inhibitory effect on telomerase activity in vitro compared with those purified by Ni-affinity chromatography. Furthermore, TLC protein could be delivered into the cell nucleus to increase the doubling time of the cell and suppress cell growth in telomerase-positive liver cancer cell lines. Cell growth inhibition was negatively correlated with telomere length, suggesting that TLC is a highly targeted telomerase-telomere anticancer agent. These results will contribute to future preclinical studies of the TLC protein.


Assuntos
Antineoplásicos/química , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Peptídeos/química , Inibidores da Transcriptase Reversa/química , Telomerase/antagonistas & inibidores , Sequência de Aminoácidos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Proliferação de Células/efeitos dos fármacos , Fermentação , Humanos , Fígado , Peptídeos/farmacologia , Proteínas Recombinantes de Fusão/química , Inibidores da Transcriptase Reversa/farmacologia , Telômero/metabolismo
10.
Nephrology (Carlton) ; 26(5): 400-407, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33484208

RESUMO

AIM: Various studies have reported that urinary neutrophil gelatinase-associated lipocalin (NGAL), an indicator of tubular damage, may be an effective biomarker of renal impairment in patients with diabetes. This study aimed to compare the ability of urinary alpha-1-microglobulin (a traditional tubular damage marker) with NGAL for evaluating renal insufficiency in patients with type-2 diabetes. METHODS: Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to determine whether 513 participants with type-2 diabetes had renal dysfunction. Urinary alpha-1-microglobulin-to-creatinine ratio (A1MCR) and NGAL-to-creatinine ratio (NCR) were calculated. RESULTS: Although both A1MCR and NCR were significantly higher among participants with renal insufficiency than among participants without renal damage, the difference in A1MCR values between participants with and without renal insufficiency was relatively greater than the difference in NCR values, especially among the male subjects. The correlation of ACR or eGFR with A1MCR was stronger than that of ACR or eGFR with NCR. A1MCR showed a good capability for detecting renal dysfunction (area under the curve = 0.80), its cut-off value was 14.82 mg/g, corresponding to 71.4% sensitivity and 73.1% specificity. The diagnostic efficiency of A1MCR was significantly higher than that of NCR. CONCLUSION: The results indicated that the traditional tubular damage marker A1MCR was more significantly associated with renal insufficiency defined by ACR and/or eGFR and may have a higher diagnostic efficiency compared with the efficiency of NCR in patients with type-2 diabetes.


Assuntos
alfa-Globulinas/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Lipocalina-2/urina , Insuficiência Renal/urina , Adulto , Idoso , Biomarcadores/urina , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/etiologia
11.
Eur J Clin Microbiol Infect Dis ; 39(4): 607-612, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31786694

RESUMO

At present, although it has made great progress in the diagnosis and treatment of tuberculosis, tuberculosis is still an important cause of morbidity and mortality. There were approximately 8.6 million new cases of tuberculosis in 2012, and approximately 1.3 million people died from tuberculosis. Early diagnosis and timely treatment are essential for controlling the spread of tuberculosis infection and reducing mortality. Conventional methods of Mycobacterium tuberculosis detection such as acid-fast staining microscopy and tuberculin skin test are widely used, but with low sensitivity or specificity. In recent years, a newly developed quantitative test, γ-interferon release test (IGRA), has been recognized and widely applied to the early diagnosis and monitoring of tuberculosis. QuantiFERON-TB Gold in-tube (QFT-GIT) is one of the mature IGRA methods. This paper summarizes the researches on QFT-GIT in recent years and introduces its principles, methodology, clinical application, and factors of uncertain results for the diagnosis and treatment of tuberculosis.


Assuntos
Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose/diagnóstico , Humanos , Tuberculose Latente/microbiologia , Mycobacterium tuberculosis/efeitos dos fármacos , Kit de Reagentes para Diagnóstico , Teste Tuberculínico , Tuberculose/microbiologia
12.
Cell Biochem Funct ; 38(7): 965-975, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32196704

RESUMO

To explore the effects of miR-21-3p on diabetic atherosclerosis. Using enzyme-linked immunosorbent assay (ELISA), we also detected the levels of soluble receptor for advanced glycation endproducts RAGE (sRAGE) in the cellular supernatant of vascular endothelial cells after transfecting them with adenovirus vector having miR-21-3p mimic or inhibitor. We found decrease in the expression levels of miR-21-3p in vascular endothelial cells (VECs) induced by high-concentration glucose. We also observed that the introduction of miR-21-3p mimic significantly increased the expression of ADAM10 in the VECs. Similarly, significantly higher levels of sRAGE were found in the cultured supernatant after administration of miR-21-3p mimic in human vein endothelial cells. The production of reactive oxygen species and expression of inflammatory cytokines in VECs induced by LPS and high-concentration glucose were significantly decreased after administration of miR-21-3p. in vivo studies revealed that intravenous injection of miR-21-3p at regular intervals would reduce the area of atherosclerotic lesion and elevate the serum levels of sRAGE in atherosclerotic diabetic mice. miR-21-3p may be beneficial in diabetic atherosclerosis by promoting the cleaved form of sRAGE and inhibition of RAGE/NADPH oxidase signalling depending on the increased expression of ADAM10. SIGNIFICANCE OF THE STUDY: We identified a novel microRNA, miR-21-3p, which is characteristically at elevated levels in serum derived from diabetic patients and responsible for target degradation of ADAM10 mRNA. Further, we show that miR-21-3p aggravates the atherosclerotic lesion via dysfunction of the ectodomain shedding of molecular binding RAGE in the diabetic atherosclerotic mice.


Assuntos
Aterosclerose/patologia , Produtos Finais de Glicação Avançada/metabolismo , MicroRNAs/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Animais , Antagomirs/metabolismo , Aterosclerose/etiologia , Linhagem Celular , Movimento Celular , Citocinas/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Glucose/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos
13.
Small ; 14(12): e1703453, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29424080

RESUMO

Although composites of organic polymers or n-type small molecule/carbon nanotube (CNT) have achieved significant advances in thermoelectric (TE) applications, p-type TE composites of small organic molecules as thick surface coating layers on the surfaces of inorganic nanoparticles still remain a great challenge. Taking advantage of in situ oxidation reaction of thieno[3,4-b]pyrazine (TP) into TP di-N-oxide (TPNO) on single-walled CNT (SWCNT) surface, a novel synthesis strategy is proposed to achieve flexible films of TE composites with narrow-bandgap (1.19 eV) small molecule coating on SWCNT surface. The TE performance can be effectively enhanced and conveniently tuned by poly(sodium-p-styrenesulfonate) content, TPNO/SWCNT mass ratio, and posttreatment by various polar solvents. The maximum of the composite power factor at room temperature is 29.4 ± 1.0 µW m-1 K-2 . The work presents a way to achieve flexible films of p-type small organic molecule/inorganic composites with clear surface coating morphology for TE application.

14.
Int Braz J Urol ; 44(1): 75-80, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29219276

RESUMO

OBJECTIVE: To present our experience in minimally invasive management of urinary tract stones in patients with urinary diversion. MATERIALS AND METHODS: We retrospectively reviewed 26 patients with urinary tract stones after cystectomy and urinary diversion. The types of urinary diversion were ileal conduit, colon conduit, ileal orthotopic neobladder in 19, 4, and 3 patients, respectively. At postoperative days 2, a plain KUB and urinary ultrasonography were performed in order to assess stone fragmentation or hydronephrosis. According to postoperative imaging, stone free rate (SFR) was defined as complete absence of fragments or residual stones less than 4mm. RESULTS: 19 patients were treated with minimally invasive percutaneous lithotripsy (MPCNL) and 2 patients required second-look MPCNL. Anterograde flexible ureteroscopy was performed in 2 patients, while in 2 patients a combined anterograde and retrograde approach was required. Three reservoir stones were treated by transurethral neo-bladder lithotripsy. Postoperative significant complications occurred in 2 patients (7.7%). The highest percentage of stone composition was struvite, as a result of chronic urinary tract infection (UTI). SFR was 88.5% (23 of 26). CONCLUSIONS: Our experience showed that MPCNL is a safe and effective treatment modality with little morbidity for renal and upper ureteral stones in patients with urinary diversion. For middle and lower ureteral stones, an anterograde approach could be also considered as a first line treatment, but a combined anterograde and retrograde approach was required when the anterograde access alone cannot provide acceptable results.


Assuntos
Litotripsia/métodos , Ureteroscopia/métodos , Cálculos Urinários/cirurgia , Derivação Urinária , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Small ; 13(23)2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28452180

RESUMO

Polymer nanocomposite (NC) hydrogels, with 3D networks composed of delaminated inorganic nanoparticles and a polymer matrix, usually display super mechanical toughness. However, the few types of inorganic materials and relatively scarce research for NC hydrogel functions seriously limit their applications. For the first time layered rare-earth hydroxide (LRH)/polyacrylamide NC hydrogels with highly tunable photoluminescence (PL) function are reported, prepared via a convenient and green in situ polymerization process. Interestingly, the NC hydrogels reveal exciting multicolored PL phenomenon (green, yellow, orange, reddish-orange to bluish violet), long luminescence lifetime, and relatively high quantum efficiency. Furthermore, the fascinating PL function is highly tunable by adjusting LRH constituent or its concentration, and excitation wavelength. The results highlight the fabrication and applications of functional polymer NC hydrogels with highly tunable PL function.

16.
J Biol Chem ; 289(10): 7099-7108, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24451375

RESUMO

A pivotal step in canonical Wnt signaling is Wnt-induced ß-catenin stabilization. In the absence of Wnt, ß-catenin is targeted for ß-transducin repeats-containing proteins (ß-TrCP)-mediated degradation due to phosphorylation by glycogen synthase kinase 3 (Gsk3). How canonical Wnt signaling regulates Gsk3 to inhibit ß-catenin proteolysis remains largely elusive. This study reveals novel key molecular events in Wnt signaling: induction of Gsk3ß ubiquitination and Gsk3ß-ß-TrCP binding. We found that Wnt stimulation induced prolonged monoubiquitination of Gsk3ß and Gsk3ß-ß-TrCP interaction. Monoubiquitination did not cause Gsk3ß degradation nor affects its enzymatic activity. Rather, increased monoubiquitination of Gsk3ß/Gsk3ß-ß-TrCP association suppressed ß-catenin recruitment of ß-TrCP, leading to long-term inhibition of ß-catenin ubiquitination and degradation.


Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Proteínas Contendo Repetições de beta-Transducina/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Estabilidade Enzimática , Técnicas de Silenciamento de Genes , Quinase 3 da Glicogênio Sintase/química , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Células HEK293 , Humanos , Camundongos , Dados de Sequência Molecular , Mutação , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
17.
Soft Matter ; 11(46): 9038-44, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26412191

RESUMO

A convenient green preparation method has been developed to achieve layered double hydroxide (LDH)/polymer nanocomposite (NC) hydrogels. In contrast to previous publications using toxic organic solvent of formamide or methanol in LDH exfoliation or anion exchange, the interlayer anion exchange and exfoliation of LDH are completed in one step with the help of an amino acid (L-serine). The LDH/polyacrylamide (PAM) NC hydrogels are achieved by a convenient exfoliation-adsorption in situ polymerization method. The exfoliation of LDH is characterized by dynamic light scattering and transmission electron microscopy. Interestingly, the developed NC hydrogels reveal ultrahigh deformability and extraordinary stretchability, confirmed by qualitative images and qualitative tensile and compression tests. The molecular mechanism for the ultrahigh deformability and extraordinary stretchability is discussed by crosslinking density, inter-crosslinking molecular weight and swelling tests. We believe that the findings reported herein will deepen our understanding towards the chemistry of network soft materials including gels, and further widen the applications of polymer hydrogels in mechanical devices such as artificial muscles, biomedical devices and drug delivery systems.

18.
Bioorg Med Chem Lett ; 25(4): 781-6, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25613678

RESUMO

A structure-activity relationship investigation of various 6-(azaindol-2-yl)pyridine-3-sulfonamides using the HCV replicon cell culture assay led to the identification of a potent series of 7-azaindoles that target the hepatitis C virus NS4B. Compound 2ac, identified via further optimization of the series, has excellent potency against the HCV 1b replicon with an EC50 of 2nM and a selectivity index of >5000 with respect to cellular GAPDH RNA. Compound 2ac also has excellent oral plasma exposure levels in rats, dogs and monkeys and has a favorable liver to plasma distribution profile in rats.


Assuntos
Hepacivirus/enzimologia , Piridinas/química , Piridinas/farmacologia , Sulfonamidas/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Animais , Antivirais/química , Antivirais/farmacologia , Cães , Hepacivirus/efeitos dos fármacos , Humanos , Macaca fascicularis , Ratos , Relação Estrutura-Atividade
19.
Biotechnol Appl Biochem ; 62(6): 868-73, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25524330

RESUMO

Medulloblastoma is the most common malignant pediatric brain tumor in children. GPR137 is a ubiquitously expressed gene in the central nervous system. It has been reported that GPR137 modulates malignant proliferation of glioma cells. However, the relationship between GPR137 and medulloblastoma is still unknown. In this study, we knocked down GPR137 in the medulloblastoma cell line Daoy via a lentivirus-based RNA interference system to explore its role in medulloblastoma. Functional analyses showed that cell proliferation and colony formation were obviously restrained in Daoy cells after GPR137 knockdown. Furthermore, knockdown of GPR137 in Daoy cells led to a significant increase in cell percentage in the G0/G1 phase but a decrease in the S phase. Additionally, the cell population in the sub-G1 phase, which represents apoptotic cells, was remarkably increased in GPR137 knockdown cells. GPR137 inhibition induced a strong proapoptotic effect in Daoy cells, as confirmed by annexin V-APC/7-AAD double staining. In conclusion, GPR137 knockdown inhibited growth of Daoy medulloblastoma cells via disturbing cell cycle progression and inducing apoptosis. Our investigation suggested that GPR137 could be a potential oncogene in medulloblastoma cells and might serve as a target for the treatment of medulloblastoma.


Assuntos
Neoplasias Cerebelares/patologia , Técnicas de Silenciamento de Genes , Inativação Gênica , Meduloblastoma/patologia , Receptores Acoplados a Proteínas G/deficiência , Receptores Acoplados a Proteínas G/genética , Apoptose/genética , Sequência de Bases , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Humanos , Lentivirus/genética , RNA Interferente Pequeno/genética
20.
J Clin Apher ; 30(3): 141-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25116073

RESUMO

Plasma exchange (PE) for the treatment of ricin toxicity has not been previously reported. Here we describe the use of PE to treat children who experienced ricin toxicity after ingesting castor beans. Seven children (median age: 8.1 years) who consumed castor beans (median: 5 beans) were treated with PE. All had bradycardia and sinus arrhythmia, and most had experienced episodes of vomiting and/or diarrhea. PE settings were blood flow, 50-80 mL/min; PE rate, 600-800 mL/h; volume of exchange, 1440-1950 mL. Median time from ingestion to PE was 73 h. All clinical symptoms disappeared and vital signs rapidly returned to normal after PE; no severe organ dysfunction occurred. All children were discharged and recovered uneventfully. Concentrations of all serum biochemical parameters significantly decreased immediately after PE. Some, but not all, of these parameters were also significantly decreased at 48 and 72 h after PE compared with before PE. Our findings suggest that PE can be an effective early intervention in the treatment of ricin toxicity due to castor bean ingestion.


Assuntos
Troca Plasmática/métodos , Plasmaferese/métodos , Ricina/intoxicação , Ricinus communis/intoxicação , Arritmia Sinusal/induzido quimicamente , Arritmia Sinusal/terapia , Gasometria , Bradicardia/induzido quimicamente , Bradicardia/terapia , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Resultado do Tratamento , Vômito
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