Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 53
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Hazard Mater ; 459: 132133, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37499492

RESUMO

Single-atom catalysts have attracted tremendous interests in peroxymonosulfate (PMS)-based advanced oxidation processes due to their maximum atom utilization and high reactivity, however the role of nitrogen-coordinated metal (MNx) sites with different metal centers remain blurred. Herein, a series of single-atom metals anchored on nitrogen-doped carbons (denoted as M-N/C, M = Fe, Co, Cu, and Mn) using zeolitic imidazolate frameworks as precursors are constructed for PMS activation. Their catalytic activity order follows Fe > Co > undoped N/C > Cu > Mn, especially the degradation rates of the eight model pollutants for Fe-N/C and Co-N/C are 2.5-22.4 and 1.5-19.5 times higher than those for undoped N/C, respectively. Moreover, the nature of catalytic metal center can govern the degradation behaviors in the coexisting water constituents. Experimental and theoretical results reveal that singlet oxygen (1O2) is the main oxidant responsible for pollutant degradation and its evolution path over FeN4 or CoN4 sites (PMS→OH*→*O→1O2) is elucidated, between which FeN4 with lower energy barrier is more conducive to 1O2 generation. This study can not only provide guidance for the development of highly active atomic M-N/C catalysts, but also lead to a better molecular-level understanding of PMS activation mechanism over MN4 sites.

2.
Bioresour Technol ; 385: 129445, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37399967

RESUMO

Polyhydroxyalkanoates (PHA) is green biodegradable natural polymer. Here PHA production from volatile fatty acids (VFAs) was investigated in sequential batch reactors inoculated with activated sludge. Single or mixed VFAs ranging from acetate to valerate were evaluated, and the dominant VFA concentration was 2 times of that of the others in the tests. Results showed that mixed substrates achieved about 1.6 times higher yield of PHA production than single substrate. The butyrate-dominated substrates maximized PHA content at 72.08% of VSS, and the valerate-dominated substrates were followed with PHA content at 61.57%. Metabolic flux analysis showed the presence of valerate in the substrates caused a more robust PHA production. There was at least 20% of 3-hydroxyvalerate in the polymer. Hydrogenophaga and Comamonas were the main PHA producers. As VFAs could be produced in anaerobic digestion of organic wastes, the methods and data here could be referred for efficient green bioconversion of PHA.


Assuntos
Poli-Hidroxialcanoatos , Poli-Hidroxialcanoatos/metabolismo , Esgotos , Ácidos Graxos Voláteis/metabolismo , Acetatos , Valeratos , Reatores Biológicos , Fermentação
3.
Sci Total Environ ; 895: 165120, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37379923

RESUMO

Chlorella culturing has the advantages in treatment of wastewater including swine wastewater from anaerobic digesters due to the product of biolipids and the uptake of carbon dioxide. However, there often exist high concentrations of antibiotics and heavy metals in swine wastewater which could be toxic to chlorella and harmful to the biological systems. This study examined the stress of cupric ion and oxytetracycline (OTC) at various concentrations on the nutrient removal and biomass growth in Chlorella vulgaris culturing in swine wastewater from anaerobic digesters, and its biochemical responses were also studied. Results showed that dynamic hormesis of either OTC concentration or cupric ion one on Chlorella vulgaris were confirmed separately, and the presence of OTC not only did not limit biomass growth and lipids content of Chlorella vulgaris but also could mitigate the toxicity of cupric ion on Chlorella vulgaris in combined stress of Cu2+ and OTC. Extracellular polymeric substances (EPS) of Chlorella vulgaris were used to explain the mechanisms of stress for the first time. The content of proteins and carbohydrates in EPS increased, and the fluorescence spectrum intensity of tightly-bound EPS (TB-EPS) of Chlorella vulgaris decreased with increasing concentration of stress because Cu2+ and OTC may be chelated with proteins of TB-EPS to form non-fluorescent characteristic chelates. The low concentration of Cu2+ (≤1.0 mg/L) could enhance the protein content and promote the activity of superoxide dismutase (SOD) while these parameters were decreased drastically under 2.0 mg/L of Cu2+. The activity of adenosine triphosphatase (ATPase) and glutathione (GSH) enhanced with the increase of OTC concentration under combined stress. This study helps to comprehend the impact mechanisms of stress on Chlorella vulgaris and provides a novel strategy to improve the stability of microalgae systems for wastewater treatment.


Assuntos
Chlorella vulgaris , Microalgas , Oxitetraciclina , Animais , Suínos , Águas Residuárias , Chlorella vulgaris/metabolismo , Oxitetraciclina/toxicidade , Oxitetraciclina/metabolismo , Carboidratos , Microalgas/metabolismo , Biomassa
4.
Bioresour Technol ; 382: 129179, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37196746

RESUMO

High concentrations of antibiotics in swine wastewater raises concerns about the potential adverse effects of anaerobic digestion (AD). Current studies mainly focused on the effects of various antibiotic concentrations. However, these studies didn't take into account the fluctuation of swine wastewater quality and the change of reactor operating conditions in practical engineering applications. In this study, it was found that in the operating systems with COD of 3300 mg/L and hydraulic retention time (HRT) of 4.4 days, the continuous addition of oxytetracycline for 30 days had no effect on the AD performance. Nevertheless, when COD and HRT were changed to 4950 mg/L and 1.5 days respectively, oxytetracycline at 2 and 8 mg/L increased the cumulative methane yield by 27% and 38% at the cost of destroying cell membrane, respectively, while oxytetracycline at 0.3 mg/L improved the performance and stability of AD. These results could be referred for practical engineering applications.


Assuntos
Oxitetraciclina , Eliminação de Resíduos Líquidos , Águas Residuárias , Animais , Anaerobiose , Antibacterianos , Reatores Biológicos , Metano , Oxitetraciclina/análise , Suínos , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/análise , Poluentes Químicos da Água/análise
5.
Bioresour Technol ; 377: 128927, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36940874

RESUMO

Acid stress in the anaerobic digestion process of liquor wastewater leads to low anaerobic treatment efficiency. Herein, chitosan-Fe3O4 was prepared, and its effects on anaerobic digestion processes under acid stress were studied. Results showed that chitosan-Fe3O4 increased the methanogenesis rate of anaerobic digestion of acidic liquor wastewater by 1.5-2.3 times and accelerated the restoration of acidified anaerobic systems. The analysis of sludge characteristics showed that chitosan-Fe3O4 promoted the secretion of proteins and humic substances in extracellular polymeric substances and increased the electron transfer activity of the system by 71.4%. Microbial community analysis indicated that chitosan-Fe3O4 enriched the abundance of Peptoclostridium, and Methanosaeta participated in direct interspecies electron transfer. Chitosan-Fe3O4 could promote the direct interspecies electron transfer pathway to maintain stable methanogenesis. These methods and results regarding the use of chitosan-Fe3O4 could be referred to for improving the efficiency of anaerobic digestion of high concentration organic wastewater under acid inhibition.


Assuntos
Quitosana , Águas Residuárias , Anaerobiose , Reatores Biológicos , Esgotos , Metano
6.
Sci Total Environ ; 866: 161411, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36623645

RESUMO

Hormesis has attracted close attention of environmental and toxicological communities over the past decades. Most studies focused on the hormesis induced by stressors in the aspect of their biotoxicity to organisms, while little research was conducted on hormesis in the aspect of biological wastewater treatment process. In this study, removal of NH4+-N and Cu2+ by S. polyrrhiza under long-term Cu2+ exposure at environmentally relevant concentrations in swine wastewater was investigated. Removal efficiencies of NH4+-N by duckweeds at 0.0, 0.1, 0.5, 1.0, 2.0 and 4.0 mg/L Cu2+ were 81.6 %, 83.7 %, 89.4 %, 74.9 %, 61.8 % and 45.1 % on day 28, however, during the initial period of cultivation (0-4 days), such hormetic effect was not observed, indicating time-dependent feature of hormesis in NH4+-N removal. The modified logistic growth model was applied to describe long-term hormesis induced by Cu2+ on NH4+-N removal and it suggested that the optimal copper exposure for ammonium removal was 0.48 mg/L. More importantly, it was found that previous exposure to low doses of Cu2+ (0-1 mg/L) could enhance NH4+-N removal performance under the second exposure. Cu2+ above 1 mg/L could switch copper bioaccumulation pattern from the Langmiur-irreversible type to reversible one, indicating risk of secondary pollution. Six components including freshly-produced humic-like substances, lignin, fulvic acid-protein complex, free amino acid-like substances, tyrosine-like substance and soluble amino acid-like substances in duckweeds were detected by parallel factor (PARAFAC) model detected. Principle component analysis (PCA) conducted on PARAFAC components suggested that enhanced synthesis of protein and growth factors intracellularly at low dose stimulation improved ammonia uptake from the environment. This study provided a novel strategy to improve treatment performance of duckweeds for copper contaminated wastewater and helped understand biochemical responses and their roles in evolutionary adaptive strategies to stresses.


Assuntos
Araceae , Águas Residuárias , Animais , Suínos , Hormese , Cobre/metabolismo , Íons/metabolismo , Aminoácidos/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-35206138

RESUMO

Duckweed (Spirodela polyrrhiza) has the potential to treat anaerobically digested swine wastewater (ADSW), but the effects of antibiotics and heavy metals in ADSW on the treatment performance and mechanism of Spirodela polyrrhiza are not clear. Herein, an experiment was conducted to investigate the effects of sulfamethazine (SMZ) and cupric ion on NH4+-N and total phosphorus (TP) removal from synthetic ADSW. The activity of superoxide dismutase (SOD) and the contents of photosynthetic pigments, vitamin E, and proteins in duckweed were also evaluated. Under the stress of SMZ, duckweed showed excellent removal efficiency of nutrients, and the results of SOD activity and photosynthetic pigments content indicated that duckweed had good tolerance to SMZ. Interestingly, a combined application of SMZ and cupric ion would inhibit the nutrient removal by duckweed, but significantly increased the contents of photosynthetic pigments, proteins, and vitamin E. In addition, the consequence indicated that high value-added protein and vitamin E products could be produced and harvested by cultivating duckweed in ADSW. Furthermore, possible degradation pathways of SMZ in the duckweed system were proposed based on the analysis with LC-MS/MS. This research proposed a novel view for using duckweed system to remove nutrients from ADSW and produce value-added products under the stress of SMZ and cupric ion.


Assuntos
Araceae , Águas Residuárias , Animais , Araceae/metabolismo , Cromatografia Líquida , Sulfametazina , Suínos , Espectrometria de Massas em Tandem
8.
Environ Health ; 21(1): 26, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35180862

RESUMO

BACKGROUND: Polycystic ovary morphology (PCOM) is an ultrasonographic finding that can be present in women with ovulatory disorder and oligomenorrhea due to hypothalamic, pituitary, and ovarian dysfunction. While air pollution has emerged as a possible disrupter of hormone homeostasis, limited research has been conducted on the association between air pollution and PCOM. METHODS: We conducted a longitudinal cohort study using electronic medical records data of 5,492 women with normal ovaries at the first ultrasound that underwent a repeated pelvic ultrasound examination during the study period (2004-2016) at Boston Medical Center. Machine learning text algorithms classified PCOM by ultrasound. We used geocoded home address to determine the ambient annual average PM2.5 exposures and categorized into tertiles of exposure. We used Cox Proportional Hazards models on complete data (n = 3,994), adjusting for covariates, and additionally stratified by race/ethnicity and body mass index (BMI). RESULTS: Cumulative exposure to PM2.5 during the study ranged from 4.9 to 17.5 µg/m3 (mean = 10.0 µg/m3). On average, women were 31 years old and 58% were Black/African American. Hazard ratios and 95% confidence intervals (CI) comparing the second and third PM2.5 exposure tertile vs. the reference tertile were 1.12 (0.88, 1.43) and 0.89 (0.62, 1.28), respectively. No appreciable differences were observed across race/ethnicity. Among women with BMI ≥ 30 kg/m2, we observed weak inverse associations with PCOM for the second (HR: 0.93, 95% CI: 0.66, 1.33) and third tertiles (HR: 0.89, 95% CI: 0.50, 1.57). CONCLUSIONS: In this study of reproductive-aged women, we observed little association between PM2.5 concentrations and PCOM incidence. No dose response relationships were observed nor were estimates appreciably different across race/ethnicity within this clinically sourced cohort.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Síndrome do Ovário Policístico , Adulto , Poluentes Atmosféricos/toxicidade , Poluição do Ar/estatística & dados numéricos , Estudos de Coortes , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Estudos Longitudinais , Masculino , Material Particulado/toxicidade , Síndrome do Ovário Policístico/diagnóstico por imagem , Síndrome do Ovário Policístico/epidemiologia
9.
J Environ Sci (China) ; 115: 330-340, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34969460

RESUMO

Nonradical reaction driven by peroxymonosulfate (PMS) based advanced oxidation processes has drawn widespread attention in water treatment due to their inherent advantages, but the degradation behavior and mechanism of organic pollutants are still unclear. In this study, the performance, intermediates, mechanism and toxicity of tetracycline (TC) degradation were thoroughly examined in the constructed magnetic nitrogen-doped porous carbon/peroxymonosulfate (Co-N/C-PMS) system. The results showed that 85.4% of TC could be removed within 15 min when Co-N/C and PMS was simultaneously added and the degradation rate was enhanced by 3.4 and 14.7 folds compared with Co-N/C or PMS alone, respectively. Moreover, the performance of Co-N/C was superior to that of most previously reported catalysts. Many lines of evidence indicated that Co-N/C-PMS system was a singlet oxygen-dominated nonradical reaction, which was less interfered by pH and water components, and displayed high adaptability to actual water bodies. Subsequently, the degradation process was elaborated on the basis of three-dimensional excitation-emission matrix spectra and liquid chromatography-mass spectrometry. At last, the toxicity of treated TC was greatly reduced by using microalgae Coelastrella sp. as ecological indicator. This study provides a promising approach based on singlet oxygen-dominated nonradical reaction for eliminating TC in water treatment.


Assuntos
Carbono , Oxigênio Singlete , Fenômenos Magnéticos , Nitrogênio , Peróxidos , Porosidade , Tetraciclina
10.
Sci Total Environ ; 816: 151635, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774959

RESUMO

Landfills are important sources of microorganisms associated with anaerobic digestion. However, the knowledge on microbiota along with their functional potential in this special habitat are still lacking. In this study, we recovered 1168 non-redundant metagenome-assembled genomes (MAGs) from nine landfill leachate samples collected from eight cities across China, spanning 42 phyla, 73 classes, 114 orders, 189 families, and 267 genera. Totally, 74.1% of 1168 MAGs could not be classified to any known species and 5.9% of these MAGs belonged to microbial dark matter phyla. Two putative novel classes were discovered from landfill leachate samples. The identification of thousands of novel carbohydrate-active enzymes showed similar richness level compared to the cow rumen microbiota. The methylotrophic methanogenic pathway was speculated to contribute significantly to methane production in the landfill leachate because of its co-occurrence with the acetoclastic and hydrogenotrophic methanogenic pathways. The genetic potential of dissimilatory nitrate reduction to ammonium (DNRA) was observed, implying DNRA may play a role in ammonium generation in landfill leachate. These findings implied that landfill leachate might be a valuable microbial resource repository and filled the previous understanding gaps for both methanogenesis and nitrogen cycling in landfill leachate microbiota. Our study provides a comprehensive genomic catalog and substantially provides unprecedented taxonomic and functional profiles of the landfill leachate microbiota.


Assuntos
Microbiota , Poluentes Químicos da Água , Humanos , Metagenoma , Metagenômica , Instalações de Eliminação de Resíduos , Poluentes Químicos da Água/análise
11.
Proc Mach Learn Res ; 193: 171-198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37786410

RESUMO

Medical treatments tailored to a patient's baseline characteristics hold the potential of improving patient outcomes while reducing negative side effects. Learning individualized treatment rules (ITRs) often requires aggregation of multiple datasets(sites); however, current ITR methodology does not take between-site heterogeneity into account, which can hurt model generalizability when deploying back to each site. To address this problem, we develop a method for individual-level meta-analysis of ITRs, which jointly learns site-specific ITRs while borrowing information about feature sign-coherency via a scientifically-motivated directionality principle. We also develop an adaptive procedure for model tuning, using information criteria tailored to the ITR learning problem. We study the proposed methods through numerical experiments to understand their performance under different levels of between-site heterogeneity and apply the methodology to estimate ITRs in a large multi-center database of electronic health records. This work extends several popular methodologies for estimating ITRs (A-learning, weighted learning) to the multiple-sites setting.

12.
Eur J Med Chem ; 217: 113379, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33756126

RESUMO

Emerging evidence suggests that cancer metabolism is closely associated to the serine biosynthesis pathway (SSP), in which glycolytic intermediate 3-phosphoglycerate is converted to serine through a three-step enzymatic transformation. As the rate-limiting enzyme in the first step of SSP, phosphoglycerate dehydrogenase (PHGDH) is overexpressed in various diseases, especially in cancer. Genetic knockdown or silencing of PHGDH exhibits obvious anti-tumor response both in vitro and in vivo, demonstrating that PHGDH is a promising drug target for cancer therapy. So far, several types of PHGDH inhibitors have been identified as a significant and newly emerging option for anticancer treatment. Herein, this comprehensive review summarizes the recent achievements of PHGDH, especially its critical role in cancer and the development of PHGDH inhibitors in drug discovery.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Neoplasias/tratamento farmacológico , Fosfoglicerato Desidrogenase/antagonistas & inibidores , Antineoplásicos/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores Enzimáticos/química , Humanos , Estrutura Molecular , Neoplasias/metabolismo , Fosfoglicerato Desidrogenase/química , Fosfoglicerato Desidrogenase/metabolismo , Estudos Retrospectivos
13.
Brain ; 143(11): 3352-3373, 2020 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-33141179

RESUMO

Parkinson's disease is a neurodegenerative disorder with a multifactorial aetiology. Nevertheless, the genetic predisposition in many families with multi-incidence disease remains unknown. This study aimed to identify novel genes that cause familial Parkinson's disease. Whole exome sequencing was performed in three affected members of the index family with a late-onset autosomal-dominant parkinsonism and polyneuropathy. We identified a novel heterozygous substitution c.941A>C (p.Tyr314Ser) in the mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene, which co-segregates with disease within the family. Additional analysis of 699 unrelated Parkinson's disease probands with autosomal-dominant Parkinson's disease and 1934 patients with sporadic Parkinson's disease revealed another two variants in UQCRC1 in the probands with familial Parkinson's disease, c.931A>C (p.Ile311Leu) and an allele with concomitant splicing mutation (c.70-1G>A) and a frameshift insertion (c.73_74insG, p.Ala25Glyfs*27). All substitutions were absent in 1077 controls and the Taiwan Biobank exome database from healthy participants (n = 1517 exomes). We then assayed the pathogenicity of the identified rare variants using CRISPR/Cas9-based knock-in human dopaminergic SH-SY5Y cell lines, Drosophila and mouse models. Mutant UQCRC1 expression leads to neurite degeneration and mitochondrial respiratory chain dysfunction in SH-SY5Y cells. UQCRC1 p.Tyr314Ser knock-in Drosophila and mouse models exhibit age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity and aberrant mitochondrial ultrastructures in nigral neurons. Furthermore, intraperitoneal injection of levodopa could significantly improve the motor dysfunction in UQCRC1 p.Tyr314Ser mutant knock-in mice. Taken together, our in vitro and in vivo studies support the functional pathogenicity of rare UQCRC1 variants in familial parkinsonism. Our findings expand an additional link of mitochondrial complex III dysfunction in Parkinson's disease.


Assuntos
Mitocôndrias/genética , Transtornos Parkinsonianos/genética , Polineuropatias/genética , Idade de Início , Idoso , Animais , Antiparkinsonianos/uso terapêutico , Linhagem Celular , Aberrações Cromossômicas , Drosophila , Complexo III da Cadeia de Transporte de Elétrons/genética , Feminino , Mutação da Fase de Leitura , Técnicas de Introdução de Genes , Genes Dominantes , Humanos , Levodopa/uso terapêutico , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação/genética , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/tratamento farmacológico , Linhagem , Polineuropatias/etiologia , Sequenciamento do Exoma
14.
Bioresour Technol ; 318: 124054, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32892026

RESUMO

This research 12 microalgal species were screened for biofilm attached culture in the treatment of anaerobically digested swine wastewater (ADSW). The influence of ADSW on biomass productivity and removal efficiencies were evaluated using biofilm attached culture with the selected Chlorella pyrenoidosa. The variation of nutritional components from algal cells were further analysed to evaluate the potential applications of C. pyrenoidosa. The results showed that C. pyrenoidosa had the highest tolerance to ADSW, and the highest removal efficiencies for wastewater pollutants were reached when cultured in 5 times diluted ADSW. These test conditions resulted in an algal cell biomass composed of 57.30% proteins, 14.87% extracellular polysaccharide, 3.08% crude fibre, 5.57% crude ash, 2.85% moisture. Amino acids in proteins contained 21.73% essential amino acids and the EAA/NEAA value was 0.64. The essential amino acid score indicates that the selected C. pyrenoidosa could be a good protein source for feed addition.


Assuntos
Chlorella , Microalgas , Animais , Biofilmes , Biomassa , Lipídeos , Suínos , Águas Residuárias/análise
15.
Front Immunol ; 11: 832, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32457754

RESUMO

Inhibitors that block the programmed cell death-1 (PD-1) pathway can potentiate endogenous antitumor immunity and have markedly improved cancer survival rates across a broad range of indications. However, these treatments work for only a minority of patients. The efficacy of anti-PD-1 inhibitors may be extended by cytokines, however, the incorporation of cytokines into therapeutic regimens has significant challenges. In their natural form when administered as recombinant proteins, cytokine treatments are often associated with low response rates. Most cytokines have a short half-life which limits their exposure and efficacy. In addition, cytokines can activate counterregulatory pathways, in the case of immune-potentiating cytokines this can lead to immune suppression and thereby diminish their potential efficacy. Improving the drug-like properties of natural cytokines using protein engineering can yield synthetic cytokines with improved bioavailability and tissue targeting, allowing for enhanced efficacy and reduced off-target effects. Using structure guided engineering we have designed a novel class of antibody-cytokine fusion proteins consisting of a PD-1 targeting antibody fused together with an interleukin-21 (IL-21) cytokine mutein. Our bifunctional fusion proteins can block PD-1/programmed death-ligand 1 (PD-L1) interaction whilst simultaneously delivering IL-21 cytokine to PD-1 expressing T cells. Targeted delivery of IL-21 can improve T cell function in a manner that is superior to anti-PD-1 monotherapy. Fusion of engineered IL-21 variants to anti-PD1 antibodies can improve the drug-like properties of IL-21 cytokine leading to improved cytokine serum half-life allowing for less frequent dosing. In addition, we show that targeted delivery of IL-21 can minimize any potential detrimental effect on local antigen-presenting cells. A highly attenuated IL-21 mutein variant (R9E:R76A) fused to a PD-1 antibody provides protection in a humanized mouse model of cancer that is refractory to anti-PD-1 monotherapy. Collectively, our preclinical data demonstrate that this approach may improve upon and extend the utility of anti-PD-1 therapeutics currently in the clinic.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Linfócitos T CD8-Positivos/imunologia , Imunoterapia , Interleucinas/uso terapêutico , Neoplasias/terapia , Animais , Anticorpos Monoclonais/imunologia , Antígeno B7-H1/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Interleucinas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Neoplasias/imunologia , Engenharia de Proteínas , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico
16.
Drug Metab Dispos ; 48(5): 408-419, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32132091

RESUMO

The objectives of the present study were to characterize GNE-947 for its phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitory activities, in vitro anti-cell migration activity in human umbilical vein endothelial cells (HUVECs), in vivo antineovascularization activity in laser-induced rat choroidal neovascular (CNV) eyes, pharmacokinetics in rabbit plasma and eyes, and ocular distribution using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) and autoradioluminography. Its PI3K and mTOR K i were 0.0005 and 0.045 µM, respectively, and its HUVEC IC50 was 0.093 µM. GNE-947 prevented neovascularization in the rat CNV model at 50 or 100 µg per eye with repeat dosing. After a single intravenous injection at 2.5 and 500 µg/kg in rabbits, its plasma terminal half-lives (t 1/2) were 9.11 and 9.59 hours, respectively. After a single intravitreal injection of a solution at 2.5 µg per eye in rabbits, its apparent t 1/2 values were 14.4, 16.3, and 23.2 hours in the plasma, vitreous humor, and aqueous humor, respectively. After a single intravitreal injection of a suspension at 33.5, 100, 200 µg per eye in rabbits, the t 1/2 were 29, 74, and 219 days in the plasma and 46, 143, and 191 days in the eyes, respectively. MALDI-IMS and autoradioluminography images show that GNE-947 did not homogenously distribute in the vitreous humor and aggregated at the injection sites after injection of the suspension, which was responsible for the long t 1/2 of the suspension because of the slow dissolution process. This hypothesis was supported by pharmacokinetic modeling analyses. In conclusion, the PI3K/mTOR inhibitor GNE-947 prevented neovascularization in a rat CNV model, with t 1/2 up to approximately 6 months after a single intravitreal injection of the suspension in rabbit eyes. SIGNIFICANCE STATEMENT: GNE-947 is a potent phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor and exhibits anti-choroidal neovascular activity in rat eyes. The duration of GNE-947 in the rabbit eyes after intravitreal injection in a solution is short, with a half-life (t 1/2) of less than a day. However, the duration after intravitreal dose of a suspension is long, with t 1/2 up to 6 months due to low solubility and slow dissolution. These results indicate that intravitreal injection of a suspension for low-solubility drugs can be used to achieve long-term drug exposure.


Assuntos
Inibidores da Angiogênese/farmacologia , Neovascularização de Coroide/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Animais , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/patologia , Modelos Animais de Doenças , Meia-Vida , Células Endoteliais da Veia Umbilical Humana , Humanos , Injeções Intravenosas , Injeções Intravítreas , Masculino , Modelos Biológicos , Soluções Oftálmicas/farmacologia , Soluções Oftálmicas/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase/química , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Coelhos , Ratos , Solubilidade , Serina-Treonina Quinases TOR/metabolismo , Distribuição Tecidual
17.
Bioresour Technol ; 297: 122516, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31830716

RESUMO

Cultivating microalgae on wastewaters is an effective way to produce algal biomass whereas harvesting microalgae is a costly operation. This study we examined the feasibility of co-culturing a high-value microalga with an auto-flocculating strain to enable efficient recovery of biomass. Experiments were conducted to co-cultivate Chlorella zofingiensis with Tribonema sp. on swine wastewater diluted by fishery wastewater under different conditions. The result showed the optimal inoculum ratio of Tribonema sp. to Chlorella zofingiensis was 1:1. The removal efficiencies of pollutants (NH4+-N, TN, TP, and COD) and lipid content were high when the co-culture ratios of Tribonema sp. were high. Also, some larger chain fatty acids, specifically C20:5 and C22:6 were present when the two strains co-culture. The recovery efficiency increased with the increasing proportion of auto-flocculating Tribonema sp.. Algae co-culture has the potential to address limitations in substrate utilization by individual strains, also improve the recovery of biomass.


Assuntos
Chlorella , Microalgas , Animais , Biomassa , Técnicas de Cocultura , Pesqueiros , Nitrogênio , Suínos , Águas Residuárias
18.
Bioresour Technol ; 297: 122385, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761625

RESUMO

This work mainly studied B. braunii adapted to different CO2 concentrations with cobalt enrichment, and developed a process for CO2 capture, hydrocarbon production and cobalt removal. The results showed that B. braunii favored rapid growth at 5.0% (v/v) CO2, and the highest biomass was 1.89 g.L-1 with 4.5 mg.L-1 of cobalt. Hydrocarbon productivity in high concentration CO2 (5.0% and 10.0%) with cobalt enrichment was higher than that in Chu 13 medium. The change in cobalt removal efficiency mainly corresponded to the growth of B. braunii. The LCE of B. braunii in cobalt-rich with high CO2 concentration (5.0% and 10.0%) was 15.7%, and 14.9%, respectively, which was higher than that in normal medium. CO2 fixation rates were also higher in cobalt enrichment coupled with high CO2 concentration. This study not only provides ideas for the removal of toxic metal cobalt, but also has great potential for CO2 biofixation.


Assuntos
Dióxido de Carbono , Clorófitas , Biomassa , Cobalto , Hidrocarbonetos
19.
Fertil Res Pract ; 5: 13, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827874

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia, oligo-anovulation, and numerous ovarian cysts. Hospital electronic medical records provide an avenue for investigating polycystic ovary morphology commonly seen in PCOS at a large scale. The purpose of this study was to develop and evaluate the performance of two machine learning text algorithms, for classification of polycystic ovary morphology (PCOM) in pelvic ultrasounds. METHODS: Pelvic ultrasound reports from patients at Boston Medical Center between October 1, 2003 and December 12, 2016 were included for analysis, which resulted in 39,093 ultrasound reports from 25,535 unique women. Following the 2003 Rotterdam Consensus Criteria for polycystic ovary syndrome, 2000 randomly selected ultrasounds were expert labeled for PCOM status as present, absent, or unidentifiable (not able to be determined from text alone). An ovary was marked as having PCOM if there was mention of numerous peripheral follicles or if the volume was greater than 10 ml in the absence of a dominant follicle or other confounding pathology. Half of the labeled data was used to develop and refine the algorithms, and the other half was used as a test set for evaluating its accuracy. RESULTS: On the evaluation set of 1000 random US reports, the accuracy of the classifiers were 97.6% (95% CI: 96.5, 98.5%) and 96.1% (94.7, 97.2%). Both models were more adept at identifying PCOM-absent ultrasounds than either PCOM-unidentifiable or PCOM-present ultrasounds. The two classifiers estimated prevalence of PCOM within the whole set of 39,093 ultrasounds to be 44% PCOM-absent, 32% PCOM-unidentifiable, and 24% PCOM-present. CONCLUSIONS: Although accuracy measured on the test set and inter-rater agreement between the two classifiers (Cohen's Kappa = 0.988) was high, a major limitation of our approach is that it uses the ultrasound report text as a proxy and does not directly count follicles from the ultrasound images themselves.

20.
Neurobiol Aging ; 84: 235.e9-235.e10, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31564376

RESUMO

Mutations in the podocalyxin-like gene (PODXL) have been recently identified in a consanguineous Indian family with juvenile-onset Parkinson's disease (PD) and 3 unrelated patients with PD. However, the pathogenicity of PODXL mutations in the disease and their role in other PD populations remain unclear. The aim of this study was to investigate the PODXL mutations in a Taiwanese cohort with familial and young-onset PD. Among 531 participants, including 161 probands from PD pedigrees without known PD-causative gene mutations and 370 patients with early-onset PD (age of onset <50 years), all exons and exon-intron boundary junctions of PODXL were analyzed by Sanger sequencing. We did not find any pathogenic coding variants or previously reported mutations, indicating that PODXL mutations may not play a role in familial or early-onset PD in this Taiwanese population.


Assuntos
Doença de Parkinson/genética , Sialoglicoproteínas/genética , Idade de Início , Humanos , Taiwan
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...