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1.
Bioresour Technol ; 305: 123031, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32126482

RESUMO

Influences of organics on partial nitritation performance were investigated in a lab-scale sequencing batch biofilm reactor filled with zeolite. Significant differences in nitrite production rate (NPR) were observed between different dosages of glucose. With influent COD/N ratio from 0 to 1.5, NPR declined from 0.4 to 0.05 kg/(m3·d). Meanwhile, an appropriate NO2--N/NH4+-N ratio (1.4 ± 0.5) could be obtained for simultaneous anammox denitrification at COD/N ratio of 0.5. Increasing airflow rate was found as an effective recovery strategy. Other than competition of heterotrophs with nitrifiers for dissolved oxygen, it has been verified that addition of organics generated higher free ammonia, and then further inhibitedammonium oxidizing bacteria (AOB). Moreover, three-dimensional excitation-emission matrix (3D-EEM) results revealed that protein-like and humic acid-like substances were the main components in extracellularpolymericsubstances (EPS). And high-throughput sequencing analysis demonstrated that the relative abundance of AOB decreased.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32207021

RESUMO

In this study, 2 (3), 9 (10), 16 (17), 23 (24)-tetrakis-(8-quinoline-oxy) phthalocyanine zinc(II) (ZnQPc) was prepared and then quaternized to obtain water soluble zinc phthalocyanine (ZnQPc4+). Then, ZnQPc4+ was used as a photosensitizer for a series of POM catalysts, including Dawson type K6[α-P2W18O62]·14H2O (P2W18) and K10[α-P2W17O61]·20H2O (P2W17) and Keggine type H3PW12O40·xH2O (PW12). The Keggin type PW12 showed higher efficiency with 18.2 µmol of H2 evolution (turnover number (TON) = 14,550) for 6 h upon ZnQPc4+ sensitization in relation to two Dawson P2W17 and P2W18 in a visible light-driven water-soluble system with isopropanol and H2PtCl6·6H2O. In addition, the complexes of ZnQPc4+ with a series of POM catalysts (P2W17, P2W18, and PW12) were also used as photocatalysts for the degradation of methylene blue (MB) in water, and it was found that the complexes of ZnQPc4+ with P2W17 and PW12 showed improved photocatalytic activity, and the degradation rates of MB reached 100% at a small dosage under natural pH and visible light. The high efficacy of POM catalysts for H2 evolution and the degradation of MB were attributed to the sensitization of POMs by ZnQPc4+, which was enabled by the transfer of photogenerated electrons of ZnQPc4+ to the lowest unoccupied molecular orbital (LUMO) of POM.

3.
Gigascience ; 9(2)2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101298

RESUMO

BACKGROUND: Color vision is the ability to detect, distinguish, and analyze the wavelength distributions of light independent of the total intensity. It mediates the interaction between an organism and its environment from multiple important aspects. However, the physicochemical basis of color coding has not been explored completely, and how color perception is integrated with other sensory input, typically odor, is unclear. RESULTS: Here, we developed an artificial intelligence platform to train algorithms for distinguishing color and odor based on the large-scale physicochemical features of 1,267 and 598 structurally diverse molecules, respectively. The predictive accuracies achieved using the random forest and deep belief network for the prediction of color were 100% and 95.23% ± 0.40% (mean ± SD), respectively. The predictive accuracies achieved using the random forest and deep belief network for the prediction of odor were 93.40% ± 0.31% and 94.75% ± 0.44% (mean ± SD), respectively. Twenty-four physicochemical features were sufficient for the accurate prediction of color, while 39 physicochemical features were sufficient for the accurate prediction of odor. A positive correlation between the color-coding and odor-coding properties of the molecules was predicted. A group of descriptors was found to interlink prominently in color and odor perceptions. CONCLUSIONS: Our random forest model and deep belief network accurately predicted the colors and odors of structurally diverse molecules. These findings extend our understanding of the molecular and structural basis of color vision and reveal the interrelationship between color and odor perceptions in nature.

4.
J Glaucoma ; 29(1): 46-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31688374

RESUMO

PRéCIS:: The overall incidence of postoperative suspected glaucoma and glaucoma after congenital cataract surgery is low; however, the identification of the associated risk factors helps to monitor susceptible individuals and to provide real-time surveillance and timely intervention. PURPOSE: Pediatric patients who have undergone surgery for congenital or infantile cataracts have a risk of developing suspected glaucoma and glaucoma, but the current evidence does not address our understanding of the incidence and associated risk factors of suspected glaucoma/glaucoma for application in clinical standard care. Therefore, this study investigated the incidence of and risk factors for suspected glaucoma/glaucoma in patients who have undergone surgery for congenital/infantile cataracts. METHODS: This study used a prospective cohort of 241 eyes from 241 patients who were 10 years of age or younger and who had undergone congenital/infantile cataract surgeries and were recruited from January 2011 to December 2016 at the Zhongshan Ophthalmic Center. Pediatric patients who underwent cataract surgery were classified into 2 groups according to intraocular lens (IOL) implantation. The patients' baseline characteristics and the incidence and risk factors for suspected glaucoma/glaucoma were assessed. RESULTS: The incidence of suspected glaucoma after cataract surgery was 10.70% [26 of 241 eyes; 95% confidence interval (CI), 6.88%-14.70%]. The rate of suspected glaucoma developing into glaucoma was 26.92% (7 of 26 eyes; 95% CI, 9.87%-43.97%), and the incidence of glaucoma was 2.90% (7 of 241 eyes; 95% CI, 0.79%-5.03%). Our study revealed that the incidence of suspected glaucoma/glaucoma in patients who did not receive IOL implantation was 13.91% (21 of 151 eyes; 95% CI, 8.39%-19.42%), and the incidence in patients who received IOL implantation was 5.56% (5 of 90 eyes; 95% CI, 8.23%-10.28%). The preoperative central corneal thickness (hazard ratio, 1.003; 95% CI, 1.001 to 1.004; P=0.004) and a family history of congenital cataracts (hazard ratio, 2.314; 95% CI, 1.004-5.331; P=0.049) were significant risk factors in patients without IOL implantation. Patient age at the time of cataract surgery was not a statistically significant risk factor for the development of suspected glaucoma/glaucoma in patients without IOL implantation. CONCLUSIONS: Identification of the incidence of and risk factors for suspected glaucoma/glaucoma may help clinicians monitor susceptible individuals and provide timely surveillance and interventions in a clinical setting. Age at the time of cataract surgery was not a risk factor for suspected glaucoma/glaucoma in patients without IOL implantation, and this may allow the timing window for pediatric cataract surgery to be expanded and support new insights into the optimal timing of surgery for standard care.

5.
Prostate ; 80(3): 256-266, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31856338

RESUMO

BACKGROUND: Because androgen receptor (AR) signaling is essential for prostate cancer (PCa) initiation and progression, castration is the main approach for treatment. Unfortunately, patients tend to enter a stage called castration-resistant prostate cancer (CRPC) despite the initial response to castration. For various reasons, AR signaling is reactivated in CRPC. As such, AR signaling inhibitors, such as enzalutamide, has been approved by the Food and Drug Administration to treat CRPC in the clinic. However, the limited success of these new drugs suggests an immediate unmet need to understand the underlying mechanisms for resistance so novel targets can be identified to enhance their efficacy. METHODS: An unbiased bioinformatics analysis was performed with the existing human patient dataset and RNA-seq results of in-house PCa cell lines to identify new targets to overcome enzalutamide resistance. Cell viability and growth were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and colony formation assay. Cell invasion and migration were detected by transwell assay. Protein levels were detected by Western blot or immunofluorescence. RESULTS: We found that the noncanonical Wnt signaling was activated in enzalutamide-resistant PCa cells and that the activation of noncanonical Wnt signaling was correlated with AR expression and disease progression. This was validated by the elevated expression of noncanonical Wnt pathway members such as Wnt5a, RhoA, and ROCK in enzalutamide-resistant PCa cells in comparison to their enzalutamide-sensitive counterparts. And, both Y27632, an inhibitor of ROCK, and depletion of ROCK enhanced the efficacy of enzalutamide in enzalutamide-resistant PCa cells. Of significance, a combination of Y27632 and enzalutamide inhibited 22RV1-derived xenograft tumor growth synergistically. Finally, ROCK depletion plus enzalutamide treatment inhibited invasion and migration of enzalutamide-resistant PCa cells via inhibition of epithelial-mesenchymal transition. CONCLUSIONS: The noncanonical Wnt pathway is activated in enzalutamide-resistant PCa and inhibition of noncanonical Wnt pathway overcomes enzalutamide resistance and enhances its efficacy in CRPC.

6.
Clin Exp Ophthalmol ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31860154

RESUMO

IMPORTANCE: There is no clear consensus on which intraocular lens (IOL) power calculation formula provides the best refractive prediction in the paediatric population. BACKGROUND: To evaluate the predictability of desired postoperative refractive outcomes by using six IOL formulas in paediatric cataract cases. DESIGN: Retrospective case series. PARTICIPANTS: A total of 377 eyes in 377 paediatric patients (<13 years of age) who received primary IOL implants in the capsular bag. METHODS: This study utilized formulas, namely, SRK II, SRK/T, Hoffer Q, Holladay 1, T2 and Super formula. Prediction errors were calculated based on the difference between the postoperative refraction and the refraction predicted by each formula. MAIN OUTCOME MEASURES: The mean prediction error, mean absolute error, median absolute error, percentages of eyes within the prediction errors of ±0.50 D, ±1.00 D and ± 2.00 D. RESULTS: The mean axial length was 22.48 ± 1.91 mm (<22.0 mm for 161 eyes). The average age at surgery was 55.21 ± 28.01 months (<24 months for 37 eyes). The mean prediction error was positive (hyperopic error) with all formulas. Compared to the other IOL power formulas, SRK II showed significantly higher absolute errors (P < .001). Hoffer Q and Holladay 1 generated the least absolute error, followed closely by Super formula. Multiple logistic analyses indicated that age at time of surgery was an independent factor significantly contributing to the refractive surprise using all formulas. CONCLUSIONS AND RELEVANCE: SRK II was the least predictable formula in this study. HofferQ and Holladay 1 yielded the best predictive values.

7.
Huan Jing Ke Xue ; 40(6): 2807-2812, 2019 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854674

RESUMO

Stable partial nitrification was successfully achieved in a zeolite sequencing batch reactor (ZSBR) with an excellent nitrite accumulation ratio of over 90.0%, and the effects of four alkalinity concentrations (calculated by CaCO3) on the nitritation in the ZSBR were investigated at an influent ammonia nitrogen concentration of 500 mg·L-1. The results showed that the key for the partial nitrification achieved in ZSBR was that the inhibitory effect of free ammonia (FA) on nitrite oxidizing bacteria (NOB) was much greater than that on ammonia oxidizing bacteria (AOB). Additionally, the wastewater containing ammonia nitrogen converted by this process can be used as the influent for anaerobic ammonium oxidation to further remove ammonia nitrogen and total nitrogen in wastewater. When the dosage of alkalinity was 2500 mg·L-1 in the ZSBR, the best nitritation efficiency was obtained with an average ammonia nitrogen conversion efficiency of 66.7%, nitrite accumulation ratio of 98.1%, and nitrite production rate of 0.74 kg·(m3·d)-1. It was demonstrated by high-throughput sequencing analysis that significant microbial community variations occurred after a long period of operation, and these changes involved an enrichment of AOB and inhibition of NOB in the ZSBR.

8.
Medicine (Baltimore) ; 98(39): e17307, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574859

RESUMO

To investigate the cognitive and psychological outcomes of pediatric allogeneic HSCT survivors in China.A total of 135 3 to 18 years old children and adolescents who underwent allo-HSCT and survived at least 3 months post-HSCT were recruited and completed the assessments. Cognitive and psychological functions were assessed via age-appropriate standardized measures. Clinical information was extracted from the medical records.Forty one 3 to 6 years old children completed Psychological Questionnaires for 3 to 6 years Children. The scores of 21(51.2%) children in cognitive development dimension, 18(43.9%) in motor development dimension, 16(39.0%) in language development and social development dimension, 15(36.6%) in emotion and will dimension and 14(34.1%) in living habits dimension were less than the standard. Fifty six 8 to 16 years old children and adolescents completed the Depression Self-rating Scale for Children and 9 (16.1%) of these met the criteria of depression. Sixty nine 7 to 16 years old children and adolescents completed the screening for Child Anxiety Related Disorders and 7 (10.1%) of these met the criteria of anxiety, especially social phobia and school phobia. Eighty nine 6 to 18 years old children and adolescents completed the Symptom Checklist-90 and 43.8% to 77.5% of these experienced mild symptoms like obsession-compulsion (77.5%), hostility (64%), and interpersonal sensitivity (60.7%). Children treated with total body irradiation (TBI) showed more cognitive impairments like motor deficits than those without TBI. Also older children and adolescents had more symptoms like psychoticism.These findings demonstrated cognitive and psychological late effects of pediatric allo-HSCT survivors in a single center in China and highlighted that the survivors conditioned with TBI had more cognitive impairments and older children and adolescents had more symptoms. Early intervention in these children and adolescents might minimize the cognitive losses and psychological effects.


Assuntos
Ansiedade , Disfunção Cognitiva , Depressão , Transplante de Células-Tronco Hematopoéticas , Complicações Pós-Operatórias , Qualidade de Vida , Adolescente , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/prevenção & controle , Criança , Pré-Escolar , China/epidemiologia , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Depressão/diagnóstico , Depressão/etiologia , Depressão/prevenção & controle , Intervenção Médica Precoce/métodos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Destreza Motora , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Técnicas Psicológicas , Sobreviventes/psicologia
9.
Br J Ophthalmol ; 103(11): 1553-1560, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31481392

RESUMO

PURPOSE: To establish and validate a universal artificial intelligence (AI) platform for collaborative management of cataracts involving multilevel clinical scenarios and explored an AI-based medical referral pattern to improve collaborative efficiency and resource coverage. METHODS: The training and validation datasets were derived from the Chinese Medical Alliance for Artificial Intelligence, covering multilevel healthcare facilities and capture modes. The datasets were labelled using a three-step strategy: (1) capture mode recognition; (2) cataract diagnosis as a normal lens, cataract or a postoperative eye and (3) detection of referable cataracts with respect to aetiology and severity. Moreover, we integrated the cataract AI agent with a real-world multilevel referral pattern involving self-monitoring at home, primary healthcare and specialised hospital services. RESULTS: The universal AI platform and multilevel collaborative pattern showed robust diagnostic performance in three-step tasks: (1) capture mode recognition (area under the curve (AUC) 99.28%-99.71%), (2) cataract diagnosis (normal lens, cataract or postoperative eye with AUCs of 99.82%, 99.96% and 99.93% for mydriatic-slit lamp mode and AUCs >99% for other capture modes) and (3) detection of referable cataracts (AUCs >91% in all tests). In the real-world tertiary referral pattern, the agent suggested 30.3% of people be 'referred', substantially increasing the ophthalmologist-to-population service ratio by 10.2-fold compared with the traditional pattern. CONCLUSIONS: The universal AI platform and multilevel collaborative pattern showed robust diagnostic performance and effective service for cataracts. The context of our AI-based medical referral pattern will be extended to other common disease conditions and resource-intensive situations.

10.
Cell Biol Int ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489995

RESUMO

New evidences suggest that long non-coding RNAs (lncRNAs) may play important roles in a variety of kidney diseases, including diabetic nephropathy (DN). Our present study investigated the potential function of LINC00462 in high glucose (HG)-induced apoptosis of renal tubular epithelial cells (RTEC) and to determine the underlying mechanism. The expression of LINC00462 in renal biopsy tissues was examined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Then, a loss of function assay was performed to determine the protective effect of LINC00462 in HG-induced RTEC damage. In addition, the downstream signaling pathway of LINC00462 was also investigated. The qRT-PCR results showed that the expression of LINC00462 was significantly up-regulated in renal biopsies from DN patients. At the same time, LINC00462 was enhanced in a glucose concentration- and time-dependent manner in human kidney (HK-2 and HKC) cells subjected to HG treatment. The knockdown of LINC00462 improved the significantly reduced cell viability of HG treatment, decreased HG-induced reactive oxygen species (ROS) and malondialdehyde levels, and up-regulated the response of antioxidant systems to ROS by increasing superoxide dismutase and catalase levels. In addition, knockdown of LINC00462 inhibited HG-induced cell apoptosis and affected the expression of apoptosis-related proteins. Most importantly, we found that knockdown of LINC00462 enhanced the expression of p-AKT. Moreover, AKT-specific inhibitor LY294002 restored the effect of LINC00462 knockdown on apoptosis. In conclusion, our study demonstrated that knockdown of LINC00462 can ameliorate oxidative stress and apoptosis in HG-induced RTEC by activating the AKT pathway, suggesting that knockdown of LINC00462 may provide a potential therapeutic approach for DN.

11.
Environ Int ; 129: 497-506, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31158596

RESUMO

BACKGROUND: Metals exposure from natural environment and pollution have been linked to cardiovascular disease (CVD). However, whether associations existing between plasma multiple metals and incident cardiovascular disease in patients with type 2 diabetes (T2D) is unknown. OBJECTIVES: We conducted a prospective cohort study to investigate whether plasma levels of metals are associated with incident CVD risk in patients with T2D. METHODS: In a prospective study of 3897 type 2 diabetes embedded in the Dongfeng-Tongji cohort, fasting blood samples were collected in 2008 at baseline and in 2013 in the first follow-up period. Plasma concentrations of 23 metals were measured by inductively coupled plasma mass spectrometry (ICP-MS). The associations between plasma metal concentrations and CVD risk in patients with T2D were investigated with Cox proportional hazards models. RESULTS: During an average of 6.2 years follow-up, 1114 participants developed CVD. In the single-metal models adjusting for established cardiovascular risk factors, plasma zinc and selenium levels were negatively and strontium was positively associated with incident CVD risk in patients with T2D. Similar results were obtained in the multiple-metal model, the HRs (95% CIs) for zinc, selenium, and strontium comparing extreme quartiles were 0.78 (95% CI: 0.65-0.93; P trend = 0.011), 0.76 (95% CI: 0.64-0.91; P trend = 0.001), and 1.51 (95% CI: 1.26-1.81; P trend <0.001), respectively. In the joint association analyses of two metals, individuals with high plasma levels of zinc and selenium had significantly lower risk of incident CVD in patients with T2D than those with low levels (HR = 0.77, 95% CI: 0.65-0.91). CONCLUSIONS: The present study suggested that plasma levels of zinc and selenium had an inverse association with incident CVD risk in patients with T2D, while strontium had a positive correlation. Plasma zinc and selenium combinedly decreased incident CVD risk in patients with T2D. Further research is still needed to verify these findings in other populations.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Metais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
12.
J Biol Chem ; 294(25): 9911-9923, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31085587

RESUMO

Enzalutamide, approved by the United States Food and Drug Administration in 2018 for the management of metastatic castration-resistant prostate cancer (CRPC), is an androgen receptor (AR) inhibitor. It blocks androgen binding to the AR, AR nuclear translocation, and AR-mediated DNA binding. Unfortunately, a considerable proportion of tumors eventually develop resistance during the treatment. The molecular mechanisms underlying enzalutamide resistance are not completely understood. Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressor complex 2, has been proposed as a prognostic marker for prostate cancer (PCa). With the goal to test whether EZH2 also plays a critical role in acquisition of enzalutamide resistance in CRPC, here we examined whether EZH2 inhibition/depletion enhances the efficacy of enzalutamide in enzalutamide-resistant PCa cells. We show that combining the EZH2 inhibitor GSK126 with enzalutamide synergistically inhibits cell proliferation and colony formation and promotes apoptosis in enzalutamide-resistant PCa cells. EZH2 depletion also overcomes enzalutamide resistance in both cultured cells and xenograft tumors. Mechanistically, we found that EZH2 directly binds to the promoter of prostate-specific antigen and inhibits its expression in enzalutamide-resistant PCa cells. In agreement, bioinformatics analysis of clinical RNA sequencing data involving GSEA indicated a strong correlation between AR and EZH2 gene expression during PCa progression. Our study provides critical insights into the mechanisms underlying enzalutamide resistance, which may offer new approaches to enhance the efficacy of enzalutamide in CRPC.

13.
Sci Rep ; 9(1): 7855, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133716

RESUMO

A systematic study on the magnetic and electrical percolation phenomena of BaTiO3 (BTO)-NiZnF2O4 (NZFO) composite films is presented in this work with the purpose of simplifying the preparation process of high-performance 1-3-type multiferroic composite films. Results show that the percolation threshold of the composite films depends on the macroscopic dimension of the material. The low-dimensional nature of the composite films results in different percolation thresholds with topological transition in vertical and horizontal directions. BTO-NZFO composite films with a grain size of 15 nm and a thickness of 100 nm exhibited a percolation threshold of 0.18 in the normal direction and a percolation threshold of 0.48 in the horizontal direction. In light of this intriguing feature, a novel multiferroic composite film with 1-3 structure and strong magnetoelectric coupling was easily prepared by a 0-3 process via controlling the NZFO content in the region between two percolation thresholds.

14.
Exp Eye Res ; 181: 302-312, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30802441

RESUMO

Cryptophthalmos is a rare congenital disorder characterized by ocular dysplasia with eyelid malformation. Complete cryptophthalmos is characterized by the presence of continuous skin from the forehead over the eyes and onto the cheek, along with complete fusion of the eyelids. In the present study, we characterized the clinical manifestations of three patients with isolated bilateral cryptophthalmos. These patients shared the same c.6499C > T missense mutation in the FRAS1-related extracellular matrix protein 2 (FREM2) gene, while each individual presented an additional nonsense mutation in the same gene (Patient #1, c.2206C > T; Patient #2, c.5309G > A; and Patient #3, c.4063C > T). Then, we used CRISPR/Cas9 to generate mice carrying Frem2R725X/R2156W compound heterozygous mutations, and showed that these mice recapitulated the human isolated cryptophthalmos phenotype. We detected FREM2 expression in the outer plexiform layer of the retina for the first time in the cryptophthalmic eyes, and the levels were comparable to the wild-type mice. Moreover, a set of different expressed genes that may contribute secondarily to the phenotypes were identified by performing RNA sequencing (RNA-seq) of the fetal Frem2 mutant mice. Our findings extend the spectrum of FREM2 mutations, and provide insights into opportunities for the prenatal diagnosis of isolated cryptophthalmos. Furthermore, our work highlights the importance of the FREM2 protein during the development of eyelids and the anterior segment of the eyeballs, establishes a suitable animal model for studying epithelial reopening during eyelid development and serves as a valuable reference for further mechanistic studies of the pathogenesis of isolated cryptophthalmos.


Assuntos
DNA/genética , Proteínas da Matriz Extracelular/genética , Síndrome de Fraser/genética , Mutação de Sentido Incorreto , Animais , Análise Mutacional de DNA , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/metabolismo , Feminino , Seguimentos , Síndrome de Fraser/diagnóstico , Síndrome de Fraser/metabolismo , Imuno-Histoquímica , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Morfogênese , Linhagem , Fenótipo , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
15.
Bioresour Technol ; 273: 487-495, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30469139

RESUMO

Ammonium (NH4+-N) adsorption capacity of zeolite varies from place to place, a unique attempt to use different zeolite as adsorbent media in sequencing biofilm batch reactor (SBBR) for maintaining appropriate free ammonia (FA) range to achieve partial nitritation. SBR filled with synthetic zeolite (SSBBR) and natural zeolite (NSBBR) were applied to evaluate the NH4+-N adsorption capacity impacts on nitrogen transformation and microbial characteristics. Significant differences in nitrite production rate (NPR) were both observed in two reactors during 4 different alkalinity ratios. The highest NPR in SSBBR and NSBBR were both obtained when the alkalinity ratio was 5:1 with the values of 1.11 and 0.90 kg N/(m3·d), respectively. According to Haldane model with inhibition by FA, the kinetics of the reaction were analyzed. High-throughput sequencing analysis results further presented that SSBBR had higher relative abundance average of nitrosobacteria in genus level, which was in favor of better partial nitritation.


Assuntos
Biofilmes , Microbiota , Adsorção , Amônia/metabolismo , Reatores Biológicos/microbiologia , Nitritos/metabolismo , Nitrogênio/metabolismo , Zeolitas/química
16.
Mol Cancer Ther ; 17(7): 1554-1565, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29716963

RESUMO

Polo-like kinase 1 (Plk1), a crucial regulator of cell-cycle progression, is overexpressed in multiple types of cancers and has been proven to be a potent and promising target for cancer treatment. In case of prostate cancer, we once showed that antineoplastic activity of Plk1 inhibitor is largely due to inhibition of androgen receptor (AR) signaling. However, we also discovered that Plk1 inhibition causes activation of the ß-catenin pathway and increased expression of c-MYC, eventually resulting in resistance to Plk1 inhibition. JQ1, a selective small-molecule inhibitor targeting the amino-terminal bromodomains of BRD4, has been shown to dramatically inhibit c-MYC expression and AR signaling, exhibiting antiproliferative effects in a range of cancers. Because c-MYC and AR signaling are essential for prostate cancer initiation and progression, we aim to test whether targeting Plk1 and BRD4 at the same time is an effective approach to treat prostate cancer. Herein, we show that a combination of Plk1 inhibitor GSK461364A and BRD4 inhibitor JQ1 had a strong synergistic effect on castration-resistant prostate cancer (CRPC) cell lines, as well as in CRPC xenograft tumors. Mechanistically, the synergistic effect is likely due to two reasons: (i) Plk1 inhibition results in the accumulation of ß-catenin in the nucleus, thus elevation of c-MYC expression, whereas JQ1 treatment directly suppresses c-MYC transcription; (ii) Plk1 and BRD4 dual inhibition acts synergistically in inhibition of AR signaling. Mol Cancer Ther; 17(7); 1554-65. ©2018 AACR.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas Nucleares/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Animais , Azepinas/administração & dosagem , Proteínas de Ciclo Celular/antagonistas & inibidores , Linhagem Celular Tumoral , Epigênese Genética/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Proteínas Nucleares/antagonistas & inibidores , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Receptores Androgênicos/genética , Transdução de Sinais/efeitos dos fármacos , Tiofenos/farmacologia , Fatores de Transcrição/antagonistas & inibidores , Triazóis/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética
17.
Environ Pollut ; 234: 396-405, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29202418

RESUMO

BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a potential risk factor for adverse birth outcomes. Epigenetic mechanisms may play a key role in which PAHs exert its effects. OBJECTIVE: Our study aimed to examine whether prenatal PAH exposure was associated with adverse birth outcomes and altered DNA methylation and to explore potential mediating roles of DNA methylation. METHODS: Ten urinary PAH metabolites were measured from 106 pregnant women during late pregnancy in a Chinese cohort study. Cord blood DNA methylation in long interspersed nucleotide element-1 (LINE-1) and Alu repetitive elements as surrogates of global DNA methylation was analyzed by bisulfite pyrosequencing. Multivariable linear regression was used to estimate the associations of urinary PAH metabolites with birth outcomes and DNA methylation, and a mediation analysis was also conducted. RESULTS: Prenatal urinary 2-hydroxynaphthalene (2-OHNa), ∑OHNa (sum of 1- and 2-OHNa), and sum of monohydroxy-PAH (∑OH-PAHs) were associated with lower birth length (e.g., -0.80%, 95% CI: -1.39%, -0.20% for the third vs. first tertile of 2-OHNa; p for trend = 0.01). Prenatal urinary 2-OHNa and 1-hydroxyphenanthrene (1-OHPh) were associated with lower Alu and LINE-1 methylation (e.g., -1.88%, 95% CI: -3.73%, -0.10% for the third vs. first tertile tertile of 2-OHNa in Alu methylation; p for trend = 0.04). Mediation analysis failed to show a mediator effect of global DNA methylation in the association between prenatal urinary OH-PAHs and birth outcomes. CONCLUSIONS: Prenatal specific PAH exposures are associated with decreased birth length and global DNA methylation. However, global DNA methylation does not mediate the associations of prenatal PAH exposure with birth outcomes. Further studies are needed to confirm the results.


Assuntos
Metilação de DNA/efeitos dos fármacos , Sangue Fetal/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/urina , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal , Adulto , Elementos Alu/genética , China , Estudos de Coortes , Epigênese Genética , Feminino , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Estudos Longitudinais , Masculino , Naftóis/efeitos adversos , Naftóis/urina , Fenantrenos/efeitos adversos , Fenantrenos/urina , Gravidez , Inquéritos e Questionários , Adulto Jovem
18.
Sci Total Environ ; 619-620: 401-409, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29156261

RESUMO

Soil water repellency (SWR) causes reduced soil water storage, enhanced runoff and reduced ecosystem productivity. Therefore, characterization of SWR is a prerequisite for effective environmental management. SWR has been reported under different soils, land uses and regions of the world, particularly in forest land and after wildfires; however, the understanding of this variable in the artificial soil of rocky slope eco-engineering is still rather limited. This study presented the characterization of SWR in the artificial soil affected by the polyacrylamide (PAM) and drought stress. There were two molecular weights of PAM, and the CK was without PAM application. Three types of soil were studied: natural soil and two types of artificial soil which have been sprayed for 1y and 5y, respectively. The drought stress experiments had three drought gradients, lasted for three weeks. Water repellency index (WRI) and soil-water contact angle (ß) were determined using intrinsic sorptivity method by measuring the water sorptivity (SW) and ethanol sorptivity (SE) in all soil samples. The results showed that (1) Polyacrylamide treatments significantly increased SW by 3% to 38%, and reduced SE by 1% to 15%, WRI by 6% to 38%, ß by 3% to 23% compared to the control group. Polyacrylamide treatments also increased water-stable aggregates content and total porosity by 22% to 33%, 11% to 20% relative to the control, while PAM with a higher molecular weight performed best. (2) The interaction between PAM and drought stress had a significant effect on WRI and ß for all soil types (P<0.01) while it only had a significant effect on SW and SE for the artificial soil (P<0.01). (3) The artificial soil had a greater WRI and ß than the natural soil.

19.
Mol Cancer Ther ; 16(3): 469-479, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28069876

RESUMO

Olaparib is an FDA-approved PARP inhibitor (PARPi) that has shown promise as a synthetic lethal treatment approach for BRCA-mutant castration-resistant prostate cancer (CRPC) in clinical use. However, emerging data have also shown that even BRCA-mutant cells may be resistant to PARPi. The mechanistic basis for these drug resistances is poorly understood. Polo-like kinase 1 (Plk1), a critical regulator of many cell-cycle events, is significantly elevated upon castration of mice carrying xenograft prostate tumors. Herein, by combination with Plk1 inhibitor BI2536, we show a robust sensitization of olaparib in 22RV1, a BRCA1-deficient CRPC cell line, as well as in CRPC xenograft tumors. Mechanistically, monotherapy with olaparib results in an override of the G1-S checkpoint, leading to high expression of Plk1, which attenuates olaparib's overall efficacy. In BRCA1 wild-type C4-2 cells, Plk1 inhibition also significantly increases the efficacy of olaparib in the presence of p53 inhibitor. Collectively, our findings not only implicate the critical role of Plk1 in PARPi resistance in BRCA-mutant CRPC cells, but also shed new light on the treatment of non-BRCA-mutant patient subgroups who might also respond favorably to PARPi. Mol Cancer Ther; 16(3); 469-79. ©2017 AACR.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Ftalazinas/farmacologia , Piperazinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Animais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Genes BRCA1 , Humanos , Concentração Inibidora 50 , Masculino , Camundongos , Terapia de Alvo Molecular , Mutação , Poli(ADP-Ribose) Polimerase-1/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Carga Tumoral/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Mater Sci Eng C Mater Biol Appl ; 71: 167-175, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27987694

RESUMO

Shikimic acid (SA) is a key raw material for the synthesis of the antiviral drug, but its extraction and separation from plants is still limited. Crosslinked poly (acryloyloxyethyltrimethyl ammonium chloride, DAC) microspheres were synthesized via inverse-phase suspension polymerization. In the synthesizing, N,N'-methylene bisacrylamide (MBA) was used as crosslinker, cyclohexane as dispersed medium and span-60 as dispersants, obtaining CPDAC gel microspheres. The effect of polymerization condition on balling performance and the characteristics of CPDAC were examined. The adsorption properties of CPDAC towards SA were mainly explored and the data of adsorption isotherm were analyzed by using Langmuir, Freundlich, Temkin, Sips and Toth models. Furthermore, the adsorption mechanism was analyzed in depth, and the adsorption thermodynamics was also investigated. The results show that in order to prepare CPDAC, water phase must be added dropwise to oil phase, and the volume ratio of oil-water is more than 2:1. The mean diameter of CPDAC decreases with increasing span-60 and accelerating agitating rate. The strong electrostatic interaction is formed between quaternary ammonium nitrogen of CPDAC and COO- of SA. The adsorption kinetic data is fitted well with pseudo-first-order model. The adsorption ability is higher in aqueous water than ethanol, reaching 108mg/g, and Toth model is more suitable for describing the actual adsorption process. The adsorption of CPDAC towards SA is dependent on the pH value of the medium. The adsorption process is exothermic, the adsorption amount decreases with the increase of temperature, and the process is driven by enthalpy. The adsorption amount decreases with the increase of salinity. The reusability of CPDAC towards SA can keep 86.1% at the sixth cycle.


Assuntos
Microesferas , Modelos Químicos , Ácido Chiquímico/química , Adsorção
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