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1.
Small ; : e2309128, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308414

RESUMO

The osmotic energy conversion properties of biomimetic light-stimulated nanochannels have aroused great interest. However, the power output performance is limited by the low light-induced current and energy conversion efficiency. Here, nanochannel arrays with simultaneous modification of ZnO and di-tetrabutylammonium cis-bis(isothiocyanato)bis(2,20-bipyridyl-4,40-dicarboxylato) ruthenium (II) (N719) onto anodic aluminum oxide (AAO) to combine the nano-confined effect and heterojunction is designed, which demonstrate rectified ion transport behavior due to the asymmetric composition, structure and charge. High cation selectivity and ion flux contribute to the high power density of ≈7.33 W m-2 by mixing artificial seawater and river water. Under light irradiation, heterojunction promoted the production and separation of exciton, enhanced cation selectivity, and improved the utilization efficiency of osmotic energy, providing a remarkable power density of ≈18.49 W m-2 with an increase of 252% and total energy conversion efficiency of 30.43%. The work opens new insights into the biomimetic nanochannels for high-performance energy conversion.

2.
Environ Sci Technol ; 58(9): 4204-4213, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38373240

RESUMO

Arsenic (As) is widely present in the environment, and virtually all bacteria possess a conserved ars operon to resist As toxicity. High selenium (Se) concentrations tend to be cytotoxic. Se has an uneven regional distribution and is added to mitigate As contamination in Se-deficient areas. However, the bacterial response to exogenous Se remains poorly understood. Herein, we found that As(III) presence was crucial for Enterobacter sp. Z1 to develop resistance against Se(IV). Se(IV) reduction served as a detoxification mechanism in bacteria, and our results demonstrated an increase in the production of Se nanoparticles (SeNPs) in the presence of As(III). Tandem mass tag proteomics analysis revealed that the induction of As(III) activated the inositol phosphate, butanoyl-CoA/dodecanoyl-CoA, TCA cycle, and tyrosine metabolism pathways, thereby enhancing bacterial metabolism to resist Se(IV). Additionally, arsHRBC, sdr-mdr, purHD, and grxA were activated to participate in the reduction of Se(IV) into SeNPs. Our findings provide innovative perspectives for exploring As-induced Se biotransformation in prokaryotes.


Assuntos
Arsênio , Arsenitos , Selênio , Selênio/farmacologia , Selênio/metabolismo , Ácido Selenioso/farmacologia , Ácido Selenioso/metabolismo , Enterobacter/metabolismo , Oxirredução
3.
Small ; 19(37): e2301512, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37154221

RESUMO

The covalent organic frameworks (COFs) membrane with ordered and confined one-dimensional channel has been considered as a promising material to harvest the salinity gradient energy from the seawater and river water. However, the application of the COFs in the field of energy conversion still faces the challenges in membrane preparation. Herein, energy harvesting is achieved by taking advantage of a COFs membrane where TpDB-HPAN is synthesized via layer-by-layer self-assembly strategy at room temperature. The carboxy-rich TpDB COFs can be expediently assembled onto the substrate with an environmental-friendly method. The increased open-circuit voltage (Voc ) endows TpDB-HPAN membrane with a remarkable energy harvesting performance. More importantly, the application perspective is also illuminated by the cascade system. With the advantages of green synthesis, the TpDB-HPAN membrane can be considered as a low-cost and promising candidate for energy conversion.

4.
Cardiovasc Drugs Ther ; 37(5): 849-863, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35471717

RESUMO

PURPOSE: Endothelial progenitor cells (EPCs) play a critical role in repairing damaged vessels and triggering ischemic angiogenesis, but their number is reduced and function is impaired under diabetic conditions. Improving EPC function has been considered a promising strategy to ameliorate diabetic vascular complications. In the present study, we aim to investigate whether and how CXCR7 agonist TC14012 promotes the angiogenic function of diabetic EPCs. METHODS: High glucose (HG) treatment was used to mimic the hyperglycemia in diabetes. Tube formation, cell scratch recovery and transwell assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and cleaved-caspase3 expression were used to evaluate the angiogenic capability, cell migration, and apoptosis of EPCs, respectively. Hind limb ischemia (HLI) model was used to appraise the ability of TC14012 in promoting diabetic ischemic angiogenesis in vivo. RESULTS: HG treatment impaired EPC tube formation and migration, and induced EPC apoptosis and oxidative damage, while TC14012 rescued tube formation and migration, and prevented HG-induced apoptosis and oxidative damage of EPCs. Furthermore, these beneficial effects of TC14012 on EPCs were attenuated by specific siRNAs against CXCR7, validating that CXCR7 is a functional target of TC14012 in EPCs. Mechanistic studies demonstrated that HG treatment reduced CXCR7 expression in EPCs, and impaired Akt and endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production; similarly, these signal impairments in HG-exposed EPCs could be rescued by TC14012. However, the protective effects of TC14012 on tube formation and migration, Akt and eNOS phosphorylation, and NO production in HG-treated EPCs were almost completely abolished by siRNAs against CXCR7 or Akt specific inhibitor wortmannin. More importantly, in vivo study showed that TC14012 administration enhanced blood perfusion recovery and angiogenesis in the ischemic hind limb and increased the EPC number in peripheral circulation of db/db mice, demonstrating the capability of TC14012 in promoting EPC mobilization and ischemia angiogenic function. CONCLUSION: TC14012 can prevent EPCs from HG-induced dysfunction and apoptosis, improve eNOS activity and NO production via CXCR7/Akt signal pathway, and promote EPC mobilization and diabetic ischemia angiogenesis.


Assuntos
Diabetes Mellitus , Células Progenitoras Endoteliais , Camundongos , Animais , Células Progenitoras Endoteliais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Isquemia/tratamento farmacológico , Isquemia/complicações , Isquemia/metabolismo , Transdução de Sinais , Movimento Celular , Neovascularização Fisiológica
5.
Acta Obstet Gynecol Scand ; 102(1): 7-14, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36397723

RESUMO

INTRODUCTION: There was limited evidence on the quality of reporting and methodological quality of prediction models using machine learning methods in preterm birth. This systematic review aimed to assess the reporting quality and risk of bias of a machine learning-based prediction model in preterm birth. MATERIAL AND METHODS: We conducted a systematic review, searching the PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disk, VIP Database, and WanFang Data from inception to September 27, 2021. Studies that developed (validated) a prediction model using machine learning methods in preterm birth were included. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement and Prediction model Risk of Bias Assessment Tool (PROBAST) to evaluate the reporting quality and the risk of bias of included studies, respectively. Findings were summarized using descriptive statistics and visual plots. The protocol was registered in PROSPERO (no. CRD 42022301623). RESULTS: Twenty-nine studies met the inclusion criteria, with 24 development-only studies and 5 development-with-validation studies. Overall, TRIPOD adherence per study ranged from 17% to 79%, with a median adherence of 49%. The reporting of title, abstract, blinding of predictors, sample size justification, explanation of model, and model performance were mostly poor, with TRIPOD adherence ranging from 4% to 17%. For all included studies, 79% had a high overall risk of bias, and 21% had an unclear overall risk of bias. The analysis domain was most commonly rated as high risk of bias in included studies, mainly as a result of small effective sample size, selection of predictors based on univariable analysis, and lack of calibration evaluation. CONCLUSIONS: Reporting and methodological quality of machine learning-based prediction models in preterm birth were poor. It is urgent to improve the design, conduct, and reporting of such studies to boost the application of machine learning-based prediction models in preterm birth in clinical practice.


Assuntos
Nascimento Prematuro , Recém-Nascido , Feminino , Humanos , Prognóstico , Projetos de Pesquisa , Aprendizado de Máquina , China , Viés
6.
Molecules ; 28(9)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37175148

RESUMO

As a non-traditional sample matrix, feather samples can be used to effectively monitor antibiotic addition and organismal residue levels in poultry feeding. Therefore, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneously determine the residue levels of 26 quinolones in poultry feathers. The feather samples were extracted by sonication with a 1% formic acid and acetonitrile mixture in a water bath at 50 °C for 30 min, purified by the adsorption of multiple matrix impurities, dried with nitrogen, redissolved, and analyzed by UPLC-MS/MS. The linearity, limit of detection (LOD), limit of quantification (LOQ), recovery and precision were calculated. The 26 antibiotics demonstrated good linearity in the linear range. The recoveries and coefficients of variation were 78.9-110% and <13.7% at standard spiked levels of 10, 100 and 200 µg/kg, respectively. The LOD and LOQ were 0.12-1.31 and 0.96-2.60 µg/kg, respectively. The method also successfully identified quinolone residues in 50 poultry feather samples. The results showed that quinolones can accumulate and stabilize for a certain period of time after transferring from the body to the feathers of poultry.


Assuntos
Quinolonas , Animais , Cromatografia Líquida , Quinolonas/análise , Aves Domésticas , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Plumas/química , Antibacterianos/análise , Extração em Fase Sólida
7.
Hepatology ; 73(6): 2206-2222, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32965675

RESUMO

BACKGROUND AND AIMS: Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin-binding sites (FGF1△HBS ) against NAFLD. APPROACH AND RESULTS: FGF1△HBS administration was effective in 9-month-old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased. FGF1△HBS reduced oxidative stress by stimulating nuclear translocation of nuclear erythroid 2 p45-related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1△HBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD-like oxidative damage and lipid accumulation could be reversed by FGF1△HBS . In palmitate-treated hepatic cells, small interfering RNA (siRNA) knockdown of Nrf2 abolished only FGF1△HBS antioxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1△HBS benefits on both oxidative stress and lipid metabolism that were FGF receptor (FGFR) 4 dependent. Further support of these in vitro findings is that liver-specific AMPK knockout abolished therapeutic effects of FGF1△HBS against high-fat/high-sucrose diet-induced hepatic steatosis. Moreover, FGF1△HBS improved high-fat/high-cholesterol diet-induced steatohepatitis and fibrosis in apolipoprotein E knockout mice. CONCLUSIONS: These findings indicate that FGF1△HBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK through hepatocyte FGFR4.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Fator 1 de Crescimento de Fibroblastos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Diabetes Mellitus Experimental , Dieta Hiperlipídica , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado , Masculino , Camundongos , Camundongos Knockout , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo , Palmitatos/farmacologia , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética
8.
J Org Chem ; 87(21): 14673-14684, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36226799

RESUMO

Pd-catalyzed hydrophosphorylation of alkynes with P(O)-H compounds provided atom-economical and oxidant-free access to alkenylphosphoryl compounds. Nevertheless, the applicable P(O)-H substrates were limited to those without a hydroxyl group except H2P(O)OH. It is also puzzling that Ph2P(O)OH could co-catalyze the reaction to improve Markovnikov selectivity. Herein, a computational study was conducted to elucidate the mechanistic origin of the phenomena described above. It was found that switchable mechanisms influenced by the acidity of substrates and co-catalysts operate in hydrophosphorylation. In addition, potential side reactions caused by the protonation of PdII-alkenyl intermediates with P(O)-OH species were revealed. The regeneration of an active Pd(0) catalyst from the resulting Pd(II) complexes is remarkably slower than the hydrophosphonylation, while the downstream reactions, if possible, would lead to phosphorus 2-pyrone. Further analysis indicated that the side reactions could be suppressed by utilizing bulky substrates or ligands or by decreasing the concentration of P(O)-OH species. The presented switchable mechanisms and side reactions shed light on the co-transformations of P(O)-H and P-OH compounds in the Pd-catalyzed hydrophosphorylation of alkynes, clarify the origin of the distinct performances of P(O)-H/OH compounds, and provide theoretical clues for expanding the applicable substrate scope of hydrophosphorylation and synthesizing cyclic alkenylphosphoryl compounds.


Assuntos
Alcinos , Paládio , Paládio/química , Catálise , Ligantes , Ácidos
9.
Molecules ; 27(15)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35956903

RESUMO

An ionic liquid-modified molecularly imprinted polymer (IL-MIP) composite with sulfamethazine as a template molecule and methyl acrylic acid and 1-aminopropyl-3-methylimidazolium bromide as functional monomers was successfully synthesized. The achieved IL-MIP was characterized and evaluated in detail and utilized in the extraction and cleanup of sulfonamides (SAs) in poultry egg samples. The results demonstrated that the IL-MIP possessed a broad reorganization toward SAs and could selectively adsorb 21 kinds of SA compounds. Furthermore, the solid-phase extraction column based on the IL-MIP was used in the extraction and cleanup of 21 SAs in eggs, and the confirmatory detection of SAs was performed using ultraperformance liquid chromatography−tandem mass spectrometry. Under optimum conditions, the limits of detection (LODs) for all SAs ranged from 0.1 ng·g−1 to 1.5 ng·g−1, and the LOD of this method was better than those of the existing methods. The recoveries of SA compounds spiked in egg samples ranged from 84.3% to 105.8%, with low relative standard deviations (<15%). The developed method based on the IL-MIP extraction and cleanup was successfully used in the detection of 21 SAs in more than 100 real poultry egg samples. The results indicated that the proposed method was suitable for detecting 21 SAs in poultry eggs.


Assuntos
Líquidos Iônicos , Impressão Molecular , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Impressão Molecular/métodos , Polímeros Molecularmente Impressos , Polímeros/química , Aves Domésticas , Extração em Fase Sólida/métodos , Sulfanilamida , Sulfonamidas/química , Espectrometria de Massas em Tandem/métodos
10.
Molecules ; 27(12)2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35745041

RESUMO

An ultra-high-performance liquid chromatography coupled with high-field quadrupole-orbitrap mass spectrometry (UHPLC-QE-MS) histological platform was used to analyze the effects of two thermal processing methods (cooking and steaming) on the nutritional metabolic components of black beans. Black beans had the most amino acids, followed by lipids and polyphenols, and more sugars. Multivariate statistical analysis indicated that heat processing significantly affected the metabolic component content in black beans, with effects varying among different components. Polyphenols, especially flavonoids and isoflavones, were highly susceptible. A total of 197 and 210 differential metabolites were identified in both raw black beans and cooked and steamed black beans, respectively. Cooking reduced the cumulative content of amino acids, lipids, polyphenols, sugars, and nucleosides, whereas steaming reduced amino acid and lipid content, slightly increased polyphenol content, and significantly increased sugar and nucleoside content. Our results indicated that metabolic components were better retained during steaming than cooking. Heat treatment had the greatest impact on amino acids, followed by polyphenols, fatty acids, sugars, and vitamins, indicating that cooking promotes the transformation of most substances and the synthesis of a few. The results of this study provide a basis for further research and development of nutritional products using black beans.


Assuntos
Aminoácidos , Polifenóis , Aminoácidos/análise , Cromatografia Líquida de Alta Pressão/métodos , Lipídeos , Espectrometria de Massas , Polifenóis/análise , Açúcares
11.
Molecules ; 27(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36234703

RESUMO

In this study, a method, based on an ultraperformance liquid chromatography coupled with high-field quadrupole orbitrap high-resolution mass spectrometry (UHPLC-QE-HF-HRMS) platform, was established for the trace determination of three major avenanthramides (AVNs). The MS conditions for determining the AVNs were optimized, and the cracking methods of avenanthramides were analyzed. The linear range of the results and the correlation coefficient were 1−2000 µg/L and >0.996, respectively. Further, the established method was employed for the determination of the AVN contents of oats at different germination times, and the results indicated that the AVN contents of Zaohua and Bayou oats increased 19.26 and 6.09 times, respectively, after germination. The total AVN content of both oat varieties reached a maximum on the fifth day of germination (153.51 ± 4.08 and 126.30 ± 3.33 µg/g for the Zaohua and Bayou oats, respectively). Furthermore, this study investigated the antiallergic and antioxidant activities of the germinated oats via hyaluronidase inhibition and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging assays. The antiallergic and DPPH-scavenging abilities of the ungerminated forms of both oat varieties were weaker. However, on the fifth day of germination, the inhibition rate of anthranilamide hyaluronidase reached 72.7% and 67.3% for the Zaohua and Bayou oat varieties, respectively. The antiallergic abilities of the oats increased significantly on the fifth day of germination in terms of their antiallergic capacities and DPPH clearance (82.67% and 77.64% for the Zaohua and Bayou oats, respectively), and the two indicators exhibited similar trends. These findings demonstrated that AVNs exhibit good antisensitivity and antioxidation properties, and the antisensitivity effect correlated positively with the AVN content.


Assuntos
Antialérgicos , Avena , Antialérgicos/análise , Antioxidantes/química , Avena/química , Grão Comestível/química , Germinação , Hialuronoglucosaminidase , ortoaminobenzoatos/química
12.
J Cell Mol Med ; 25(6): 3091-3102, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33599110

RESUMO

Diabetic vascular complications are closely associated with long-term vascular dysfunction and poor neovascularization. Endothelial progenitor cells (EPCs) play pivotal roles in maintaining vascular homeostasis and triggering angiogenesis, and EPC dysfunction contributes to defective angiogenesis and resultant diabetic vascular complications. Fibroblast growth factor 21 (FGF21) has received substantial attention as a potential therapeutic agent for diabetes via regulating glucose and lipid metabolism. However, the effects of FGF21 on diabetic vascular complications remain unclear. In the present study, the in vivo results showed that FGF21 efficiently improved blood perfusion and ischaemic angiogenesis in both type 1 and type 2 diabetic mice, and these effects were accompanied by enhanced EPC mobilization and infiltration into ischaemic muscle tissues and increases in plasma stromal cell-derived factor-1 concentration. The in vitro results revealed that FGF21 directly prevented EPC damage induced by high glucose, and the mechanistic studies demonstrated that nicotinamide adenine dinucleotide (NAD+ ) was dramatically decreased in EPCs challenged with high glucose, whereas FGF21 treatment significantly increased NAD+ content in an AMPK-dependent manner, resulting in improved angiogenic capability of EPCs. These results indicate that FGF21 promotes ischaemic angiogenesis and the angiogenic ability of EPCs under diabetic conditions by activating the AMPK/NAD+ pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Células Progenitoras Endoteliais/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , NAD/metabolismo , Neovascularização Fisiológica , Animais , Biomarcadores , Diabetes Mellitus Experimental , Glucose/metabolismo , Membro Posterior/irrigação sanguínea , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Imunofenotipagem , Isquemia/metabolismo , Masculino , Camundongos , Modelos Biológicos , Transdução de Sinais
13.
Lab Invest ; 101(10): 1371-1381, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34239033

RESUMO

Sepsis is an acute inflammatory reaction and a cause of acute respiratory distress syndrome (ARDS). In the present study, we explored the roles and underlying mechanism of the lncRNA Nuclear enriched abundant transcript 1 (NEAT1) in ARDS. The expression levels of genes, proteins and pro-inflammatory cytokines in patients with ARDS, LPS-stimulated cells and septic mouse models were quantified using qPCR, western blotting and ELISA assays, respectively. The molecular targeting relationship was validated by conducting a dual-luciferase reporter assay. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The cell cycle phase was determined by flow cytometry assay. The expression levels of NEAT1 and pro-inflammatory cytokines were higher in patients with ARDS and septic models than in controls. Knockdown of NEAT1 significantly increased cell proliferation and cycle progression and prolonged mouse survival in vitro and in vivo. Mechanistically, miR-27a was identified as a downstream target of NEAT1 and directly inhibited PTEN expression. Further rescue experiments revealed that inhibition of miR-27a impeded the promoting effects of NEAT1 silence on cell proliferation and cycle progression, whereas inhibition of PTEN markedly weakened the inhibitory effects of NEAT1 overexpression on cell proliferation and cycle progression. Altogether, our study revealed that NEAT1 plays a promoting role in the progression of ARDS via the NEAT1/miR-27a/PTEN regulatory network, providing new insight into the pathologic mechanism behind ARDS.


Assuntos
MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante , Síndrome do Desconforto Respiratório/metabolismo , Sepse/metabolismo , Adulto , Animais , Linhagem Celular , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética
14.
Metab Eng ; 67: 403-416, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34411702

RESUMO

Malonyl-CoA is an important building block for microbial synthesis of numerous pharmaceutically interesting or fatty acid-derived compounds including polyketides, flavonoids, phenylpropanoids and fatty acids. However, the tightly regulated intracellular malonyl-CoA availability often impedes overall product formation. Here, in order to unleash this tightly cellular behavior, we present evolution: dual dynamic regulations-based approaches to write artificial robust and dynamic function into intricate cellular background. Firstly, a conserved core domain based evolutionary principles were incorporated into genome mining to explore the biosynthetic diversities of discrete acetyl-CoA carboxylase (ACC) families, as malonyl-CoA is solely derived from carboxylation of acetyl-CoA by ACC in most organisms. A comprehensive phylogenomic and further experimental analysis, which included genomes of 50 strains throughout representative species, was performed to recapitulate the evolutionary history and reveal that previously unnoticed ACC families from Salmonella enterica exhibited the highest activities among all the candidates. A set of orthogonal and bi-functional quorum-sensing (QS)-based regulation tools were further designed and connected with T7 RNA polymerase as genetic amplifier to achieve dual dynamic control in a high dynamic range, which allowed us to efficiently activate and repress different sets of genes dynamically and independently. These genetic circuits were then combined with ACC of S. enterica and CRISPRi system to reprogram central metabolism that rewired the tightly regulated malonyl-CoA pathway to a robust and autonomous behavior, leading to a 29-fold increase of malony-CoA availability. We applied this dual regulation tool to successfully synthesizing malonyl-CoA-derived compound (2S)-naringenin, and achieved the highest production (1073.8 mg/L) reported to date associate with dramatic decreases of by-product formation. Notably, the whole fermentation presents as an autonomous behavior, totally eliminating human supervision and inducer supplementation. Hence, the constructed evolution: dual dynamic regulations-based approaches pave the way to develop an economically viable and scalable procedure for microbial production of malonyl-CoA derived compounds.


Assuntos
Malonil Coenzima A , Policetídeos , Acetilcoenzima A/genética , Acetil-CoA Carboxilase , Engenharia Metabólica
15.
Soft Matter ; 17(43): 9866-9870, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34724018

RESUMO

6,6'-Dibromided tert-butyloxycarbonyl isoindigo (Br-TBOCII) has intense fluorescence in the solid state via excitation with aggregation-induced emission (AIE), contrary to the classic heavy-atom effect. The unique AIE mechanism is attributed to the Br-Br bonding joint restricting intramolecular motion. Furthermore, the water-soluble nanoparticles Br-TBOCII/Pluronic® 127, possess robust photostability, low toxicity and good cell imaging performance.


Assuntos
Corantes Fluorescentes , Nanopartículas , Fluorescência , Indóis
16.
J Enzyme Inhib Med Chem ; 36(1): 1563-1572, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34281464

RESUMO

A series of tertiary sulphonamide derivatives were synthesised and evaluated for their antiproliferative activity against liver cancer cell lines (SNU-475, HepG-2, and Bel-7402). Among these tertiary sulphonamides, compound 17a displayed the best anti-liver cancer activity against Bel-7402 cells with an IC50 value of 0.32 µM. Compound 17a could effectively inhibit tubulin polymerisation with an IC50 value of 1.27 µM. Meanwhile, it selectively suppressed LSD1 with an IC50 value of 63 nM. It also concentration-dependently inhibited migration against Bel-7402 cells. Importantly, tertiary sulphonamide 17a exhibited the potent antitumor activity in vivo. All these findings revealed that compound 17a might be a tertiary sulphonamide-based dual inhibitor of tubulin polymerisation and LSD1 to treat liver cancer.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Neoplasias Hepáticas/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Sulfonamidas/farmacologia , Moduladores de Tubulina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Histona Desmetilases/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Estrutura Molecular , Polimerização/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química
17.
Pediatr Emerg Care ; 37(7): 357-359, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31219969

RESUMO

OBJECTIVES: Acute late-presenting congenital diaphragmatic hernia (CDH) might result in mediastinal shift away from the lesion and even sudden cardiopulmonary arrest. This study aimed to discuss the prompt and effective emergency management of acute late-presenting CDH. METHODS: A retrospective review of acute late-presenting CDH cases in West China Hospital of Sichuan University and Guizhou Provincial People's Hospital from October 2010 to June 2016 was conducted. RESULTS: A total of 22 patients were included in this study. All the patients presented with respiratory symptoms. Chest x-ray revealed swollen stomach and mediastinal shift. After nasogastric tube placement, fluid infusion, and nasal oxygen breathing, the symptoms in 8 patients ameliorated, and 14 patients had no signs of obvious relief. Three patients underwent the bedside percutaneous puncture of distensible stomach, and 1 patient died in the process of emergent management for critical condition. The remaining 21 patients underwent emergency surgery. Five thoracotomies and 16 thoracoscopies were performed. Five thoracoscopies that were converted to thoracotomies were required for the difficult reduction of herniated stomach. At follow-up, all patients improved their condition. CONCLUSIONS: Acute late-presenting CDH is a clinical emergency that can be fatal. The sudden and progressive expansion of the stomach is mainly responsible for this emergent condition. The prompt and effective management is key to decrease the mortality and achieve favorable prognosis.


Assuntos
Parada Cardíaca , Hérnias Diafragmáticas Congênitas , Criança , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Lactente , Estudos Retrospectivos , Toracoscopia , Toracotomia
18.
J Sci Food Agric ; 101(5): 2063-2071, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32974959

RESUMO

BACKGROUND: Combination drying is recognized as an energy-efficient method utilized for dry product processing, and proper order of combination is a critical factor determining the effectiveness of the technique. In this study, hot air drying (HD), vacuum freeze-drying (VFD), and combination drying with different orders (HD-VFD and VFD-HD) are performed on whole Lentinula edodes and pre-cut (half-cut and quarter-cut) L. edodes. The effects of various cutting and drying approaches on drying characteristics, physicochemical properties, and microstructures of dried L. edodes were investigated. RESULTS: The longest processing time required to dry the whole L. edodes by VFD was 25 h. In contrast, the pre-cutting treatment and combination drying certainly shortened the drying time. Compared with HD, use of VFD-HD and VFD significantly decreased the shrinkage ratio, hardness, and discoloration of dried products but increased the rehydration capacity, nutrient retention, and porous microstructure. Interestingly, switching the order of combination drying provoked entirely different drying effects. Specifically, HD-VFD triggered negative effects on the shrinkage and color of dried mushrooms, and its appearance color was similar to HD-treated samples. Moreover, pre-cutting dramatically enhanced the protein content of HD-treated mushrooms, and the quarter-cut samples obtained the highest level (21.69 g kg-1 dry basis) among the three types of cutting. CONCLUSIONS: The dried L. edodes processed through pre-cutting and combination drying (VFD-HD) have optimal industrial quality, accompanied by shorter processing time. © 2020 Society of Chemical Industry.


Assuntos
Dessecação/métodos , Conservação de Alimentos/métodos , Cogumelos Shiitake/química , Cor , Dessecação/instrumentação , Conservação de Alimentos/instrumentação , Carpóforos/química , Dureza , Vácuo
19.
J Cell Mol Med ; 24(10): 5605-5614, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32239650

RESUMO

Endothelial progenitor cells (EPCs) are able to trigger angiogenesis, and pro-inflammatory cytokines have beneficial effects on angiogenesis under physiological and pathological conditions. C-X-C chemokine receptor type 7 (CXCR-7), receptor for stromal cell-derived factor-1, plays a critical role in enhancing EPC angiogenic function. Here, we examined whether CXCR7 mediates the pro-angiogenic effects of the inflammatory cytokine interleukin-1ß (IL-1ß) in EPCs. EPCs were isolated by density gradient centrifugation and angiogenic capability was evaluated in vitro by Matrigel capillary formation assay and fibrin gel bead assay. IL-1ß elevated CXCR7 expression at both the transcriptional and translational levels in a dose- and time-dependent manner, and blockade of the nuclear translocation of NF-κB dramatically attenuated the IL-1ß-mediated up-regulation of CXCR7 expression. IL-1ß stimulation significantly promoted EPCs tube formation and this effect was largely impaired by CXCR7-siRNA transfection. IL-1ß treatment stimulated extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and inhibition of Erk1/2 phosphorylation partially impaired IL-1ß-induced tube formation of EPCs but without significant effects on CXCR7 expression. Moreover, blocking NF-κB had no significant effects on IL-1ß-stimulated Erk1/2 phosphorylation. These findings indicate that CXCR7 plays an important role in the IL-1ß-enhanced angiogenic capability of EPCs and antagonizing CXCR7 is a potential strategy for inhibiting angiogenesis under inflammatory conditions.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo , Neovascularização Patológica/metabolismo , Receptores CCR7/metabolismo , Biomarcadores , Células Cultivadas , Células Progenitoras Endoteliais/efeitos dos fármacos , Humanos , Interleucina-1beta/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Modelos Biológicos , Transdução de Sinais/efeitos dos fármacos
20.
Anal Chem ; 92(9): 6727-6733, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32264669

RESUMO

Heparin (Hep), widely used in clinics as an anticoagulant drug, has high degrees of heterogeneity and shares a similar disaccharide repeating unit with its GAG analogues. The development of reliable and convenient methods to discriminate Hep from its GAG analogues and detect trace GAG contaminants in Hep is meaningful for safe usage of Hep in clinics. Herein, five porphyrin-GO nanocomposites denoted as PP1-GO, PP2a-GO, PP2b-GO, PP3-GO, and PP4-GO were synthesized by assembling corresponding positively charged porphyrins onto the surface of GO. Controlled by a different number and position of the 4-N-methyl-pyridyl groups substituted at the porphyrins, these nanocomposites were determined to be cross-reactive toward Hep and other three commonly used GAGs including Chs, HA, and DS. A NIR sensor array PP-GO was thus constructed using these nanocomposites for GAGs discrimination and Hep quality control through pattern-based recognition. HCA and LDA calculated results indicated that PP-GO was powerful for discrimination of Hep and its GAG analogues in both PBS and even 10% serum media. Moreover, the PP-GO sensor array was successfully applied for the reliable discrimination of trace GAG contaminants in Hep with 100% accuracy.

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