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1.
BMC Microbiol ; 23(1): 99, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-37046215

RESUMO

BACKGROUND: As highly-conserved types of lipid flippases among fungi, P4-ATPases play a significant role in various cellular processes. Cdc50 acts as the regulatory subunit of flippases, forming heterodimers with Drs2 to translocate aminophospholipids. Cdc50 homologs have been reported to be implicated in protein trafficking, drug susceptibility, and virulence in Saccharomyces cerevisiae, Candida albicans and Cryptococcus neoformans. It is likely that Cdc50 has an extensive influence on fungal cellular processes. The present study aimed to determine the function of Cdc50 in Candida glabrata by constructing a Δcdc50 null mutant and its complemented strain. RESULTS: In Candida glabrata, the loss of Cdc50 led to difficulty in yeast budding, probably caused by actin depolarization. The Δcdc50 mutant also showed hypersensitivity to azoles, caspofungin, and cell wall stressors. Further experiments indicated hyperactivation of the cell wall integrity pathway in the Δcdc50 mutant, which elevated the major cell wall contents. An increase in exposure of ß-(1,3)-glucan and chitin on the cell surface was also observed through flow cytometry. Interestingly, we observed a decrease in the phagocytosis rate when the Δcdc50 mutant was co-incubated with THP-1 macrophages. The Δcdc50 mutant also exhibited weakened virulence in nematode survival tests. CONCLUSION: The results suggested that the lipid flippase subunit Cdc50 is implicated in yeast budding and cell wall integrity in C. glabrata, and thus have a broad influence on drug susceptibility and virulence. This work highlights the importance of lipid flippase, and offers potential targets for new drug research.


Assuntos
Adenosina Trifosfatases , Saccharomyces cerevisiae , Adenosina Trifosfatases/metabolismo , Saccharomyces cerevisiae/metabolismo , Candida glabrata/genética , Candida glabrata/metabolismo , Caspofungina , Parede Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
2.
Molecules ; 28(8)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37110868

RESUMO

Heme b, which is characterized by a ferrous ion and a porphyrin macrocycle, acts as a prosthetic group for many enzymes and contributes to various physiological processes. Consequently, it has wide applications in medicine, food, chemical production, and other burgeoning fields. Due to the shortcomings of chemical syntheses and bio-extraction techniques, alternative biotechnological methods have drawn increasing attention. In this review, we provide the first systematic summary of the progress in the microbial synthesis of heme b. Three different pathways are described in detail, and the metabolic engineering strategies for the biosynthesis of heme b via the protoporphyrin-dependent and coproporphyrin-dependent pathways are highlighted. The UV spectrophotometric detection of heme b is gradually being replaced by newly developed detection methods, such as HPLC and biosensors, and for the first time, this review summarizes the methods used in recent years. Finally, we discuss the future prospects, with an emphasis on the potential strategies for improving the biosynthesis of heme b and understanding the regulatory mechanisms for building efficient microbial cell factories.


Assuntos
Heme , Porfirinas , Heme/metabolismo , Vias Biossintéticas , Porfirinas/metabolismo , Engenharia Metabólica/métodos
3.
Cell Biol Int ; 46(11): 1834-1840, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35870168

RESUMO

The objective of the study was to investigate the expression levels of potassium voltage-gated channel subfamily A member 5 (KCNA5), connexin 43 (Cx43), and connexin 40 (Cx40) in the left atrial appendage of patients with atrial fibrillation (AF) and the interactions between them. We gathered tissue samples from patients with persistent AF and sinus rhythm and used fluorescence quantitative polymerase chain reaction to evaluate messenger RNA (mRNA) changes of KCNA5, Cx43, and Cx40. Then, we studied the protein levels of KCNA5, Cx43, and Cx40 by immunofluorescence and western blot analysis and the interactions between these proteins were identified by immunoprecipitation and immunofluorescence colocation, respectively. Compared with the control group, the mRNA and protein levels of KCNA5, Cx43, and Cx40 in the AF group were decreased and the positive expression of KCNA5, Cx43, and Cx40 protein was also decreased by immunofluorescence staining in the AF group. In addition, immunoprecipitation and immunofluorescence colocation revealed that KCNA5 was coexpressed with Cx43 and Cx40 proteins. The expressions of KCNA5, Cx43, and Cx40 were substantially downregulated in the myocardium of patients with AF and KCNA5 interacted with Cx43 and Cx40 proteins, respectively.


Assuntos
Fibrilação Atrial , Conexina 43 , Conexinas/metabolismo , Fibrilação Atrial/genética , Fibrilação Atrial/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Humanos , Canal de Potássio Kv1.5/genética , Miocárdio/metabolismo , Potássio/metabolismo , RNA Mensageiro/genética
4.
Cerebrovasc Dis ; 50(5): 520-525, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34175842

RESUMO

BACKGROUND AND PURPOSE: Most patients cannot receive intravenous thrombolytic therapy in the early stage of stroke onset, and the application of mobile stroke unit (MSU) in prehospital intravenous thrombolytic therapy of acute stroke may change this situation. The first MSU in China was put into use in 2017. Herein, we aimed to explore the preliminary experience of MSU in prehospital thrombolysis of acute stroke. METHODS: Patients who received prehospital intravenous thrombolytic therapy using MSU were classified to the MSU thrombolysis group, and the control group consisted of stroke patients admitted by regular ambulances, who were transferred to hospital for intravenous thrombolytic therapy. The feasibility, safety, and duration of procedures were compared. RESULTS: There were 14 patients received prehospital intravenous thrombolysis on the MSU, and 24 patients underwent intravenous thrombolysis in the emergency center, who were transferred by the ordinary ambulance during the same period. The median call-to-needle time was 59.5 min in the MSU thrombolysis group, while it was 89 min in the control group; the difference between the 2 groups was statistically significant (p = 0.001). The median time from onset to thrombolysis was 70 and 102.5 min, respectively, in the 2 groups (p = 0.002). The percentages of good clinical outcome (modified Rankin Scale score ≤ 2) at 90-day follow-up were 79 and 67%, respectively (p = 0.488). The rate of symptomatic intracranial hemorrhage and mortality during the perioperative period did not differ significantly between 2 groups. CONCLUSION: Despite the small sample size, our preliminary experience of the application of MSU in the prehospital thrombosis therapy seems to indicate a significant reduction in time from call to needle, the efficacy of MSU in the treatment of acute stroke needs further experiment and larger sample size to confirm.


Assuntos
Serviços Médicos de Emergência , Fibrinolíticos/administração & dosagem , AVC Isquêmico/tratamento farmacológico , Unidades Móveis de Saúde , Terapia Trombolítica , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Avaliação da Deficiência , Estudos de Viabilidade , Feminino , Fibrinolíticos/efeitos adversos , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Tempo para o Tratamento , Resultado do Tratamento
5.
Environ Sci Technol ; 52(21): 12612-12623, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30252454

RESUMO

Phosphate is commonly added to drinking water to inhibit lead release from lead service lines and lead-containing materials in premise plumbing. Phosphate addition promotes the formation of lead phosphate particles, and their aggregation behaviors may affect their transport in pipes. Here, lead phosphate formation and aggregation were studied under varied aqueous conditions typical of water supply systems. Under high aqueous PO4/Pb molar ratios (>1), phosphate adsorption made the particles more negatively charged. Therefore, enhanced stability of lead phosphate particles was observed, suggesting that although addition of excess phosphate can lower the dissolved lead concentrations in tap water, it may increase concentrations of particulate lead. Adsorption of divalent cations (Ca2+ and Mg2+) onto lead phosphate particles neutralized their negative surface charges and promoted their aggregation at pH 7, indicating that phosphate addition for lead immobilization may be more efficient in harder waters. The presence of natural organic matter (NOM, ≥ 0.05 mg C/L humic acid and ≥ 0.5 mg C/L fulvic acid) retarded particle aggregation at pH 7. Consequently, removal of organic carbon during water treatment to lower the formation of disinfection-byproducts (DBPs) may have the additional benefit of minimizing the mobility of lead-containing particles. This study provided insight into fundamental mechanisms controlling lead phosphate aggregation. Such understanding is helpful to understand the observed trends of total lead in water after phosphate addition in both field and pilot-scale lead pipe studies. Also, it can help optimize lead immobilization by better controlling the water chemistry during phosphate addition.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Substâncias Húmicas , Chumbo , Abastecimento de Água
6.
Bioorg Med Chem Lett ; 24(13): 2802-6, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24835199

RESUMO

Human acrosin is an attractive target for the discovery of novel male contraceptives. Isoxazole derivative ISO-1, a small-molecule weak human acrosin inhibitor, was used as the starting point for lead optimization. After two rounds of structure-based inhibitor design, a highly potent inhibitor B6 (IC50=1.44 µM) was successfully identified, which showed good selectivity over trypsin and represents one of the most active human acrosin inhibitors up to date.


Assuntos
Acrosina/antagonistas & inibidores , Desenho de Fármacos , Isoxazóis/química , Isoxazóis/farmacologia , Acrosina/metabolismo , Relação Dose-Resposta a Droga , Humanos , Isoxazóis/síntese química , Masculino , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
7.
Chem Commun (Camb) ; 60(32): 4298-4301, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38530709

RESUMO

This study effectively addresses the challenge of nitrogen adsorption and activation in photocatalytic nitrogen fixation by introducing an oxidizing co-catalyst, NiFeB hydroxides. The NiFeB hydroxides could provide reactive active sites and significantly enhance the nitrogen oxidation activity, offering a novel pathway for co-catalysts in nitrogen fixation reactions.

8.
Turk J Biol ; 48(1): 46-58, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665782

RESUMO

Background/aim: Circular RNAs can serve as detection biomarkers and therapeutic targets for tumors. Our study aimed to elucidate the mechanisms associated with circRNA LDLR (circLDLR) in gastric cancer (GC) proliferation and aerobic glycolysis. Materials and methods: Expression signatures of circLDLR, miR-449b-5p, and CHD1 were examined in GC samples using quantitative PCR. Proliferation ability of MKN-45 cells was assessed via CCK-8 and EdU assays, and cell apoptosis was measured by flow cytometry. Glucose uptake, lactate production, ATP/ADP ratios, and NAD+/NADH ratios in cell supernatants were quantified to evaluate aerobic glycolysis. Subcellular isolation assay, quantitative PCR, immunoblot analysis, RNA immunoprecipitation (RIP), and dual luciferase reporter assay were employed to investigate the relationship between genes. Results: Expression of circLDLR and CHD1 was elevated, while miR-449b-5p expression decreased in GC. Functionally, overexpression of circLDLR enhanced proliferation and aerobic glycolysis and hampered apoptosis of MKN-45 cells. However, upregulation of miR-449b-5p or downregulation of CHD1 reversed these effects. CircLDLR acted as an miRNA spongeand regulated the expression of miR-449b-5p, thereby affecting CHD1 and accelerating GC malignant progression. Conclusion: CircLDLR drives the proliferation and aerobic glycolysis of GC cells by targeting CHD1 with miR-449b-5p, which is an ideal potential target for early diagnosis and clinical treatment of GC.

9.
Front Cardiovasc Med ; 11: 1392548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39228663

RESUMO

Backgrounds: Atrial fibrillation (AF) is a common complication of chronic heart failure (HF). Serum phenylalanine (Phe) levels are related to inflammation disorder. It is meaningful to study the circulating Phe with AF occurrence in HF. Methods: The cross-sectional study recruited 300 patients (78.0% male; mean age, 65 ± 13 years) with HF (left ventricular ejection fraction of ≤50%, containing 70 AF patients) and 100 normal controls. Serum Phe value was measured by liquid chromatography-tandem mass spectrometry. Logistic regression analysis was conducted to measure the association between Phe and AF risk in HF. The association between Phe and high-sensitivity C-reactive protein (hsCRP) was assessed by simple correlation analysis. In the prospective study, the 274 HF subjects (76.6% male; mean age, 65 ± 13 years) were followed up for a mean year (10.99 ± 3.00 months). Results: Serum Phe levels increased across the control, the HF without AF, and the HF with AF groups (77.60 ± 8.67 umol/L vs. 95.24 ± 28.58 umol/L vs. 102.90 ± 30.43 umol/L, ANOVA P < 0.001). Serum Phe value was the independent risk factor for predicting AF in HF [odds ratio (OR), 1.640; 95% CI: 1.150-2.339; P = 0.006]. Phe levels were correlated positively with hsCRP value in HF patients with AF (r = 0.577, P < 0.001). The elevated Phe levels were associated with a higher risk of HF endpoint events in HF patients with AF (log-rank P = 0.005). Conclusions: In HF with AF subjects, elevated Phe value confers an increased risk for prediction AF and was more related to poor HF endpoint events. Phe can be a valuable index of AF in HF.

10.
Bioorg Med Chem Lett ; 23(14): 4177-84, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23746472

RESUMO

A series of novel 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives were designed, synthesized, and their acrosin inhibitory activities in vitro were evaluated. The results of the acrosin inhibitory activity showed that all target compounds were more potent than control TLCK. Compounds AQ-A1, AQ-D3, AQ-D4, AQ-E4 and AQ-E5 exhibited stronger acrosin inhibitory activities than control ISO-1. Especially, compound AQ-E5 displayed the most potent acrosin inhibitory activity in all the compounds, with an IC50 of 0.01µmol/mL. This study provided a new structural class for the development of novel acrosin inhibitory agents.


Assuntos
Amidas/química , Inibidores de Proteases/síntese química , Pirazóis/química , Pirazóis/síntese química , Acrosina/antagonistas & inibidores , Acrosina/metabolismo , Amidas/síntese química , Amidas/farmacocinética , Sítios de Ligação , Domínio Catalítico , Cristalografia por Raios X , Meia-Vida , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Inibidores de Proteases/farmacocinética , Pirazóis/farmacocinética
11.
Adv Sci (Weinh) ; 10(9): e2206622, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36710254

RESUMO

Shewanella oneidensis is able to carry out extracellular electron transfer (EET), although its EET efficiency is largely limited by low flavin concentrations, poor biofilm forming-ability, and weak biofilm conductivity. After identifying an important role for riboflavin (RF) in EET via in vitro experiments, the synthesis of RF is directed to 837.74 ± 11.42 µm in S. oneidensis. Molecular dynamics simulation reveals RF as a cofactor that binds strongly to the outer membrane cytochrome MtrC, which is correspondingly further overexpressed to enhance EET. Then the cell division inhibitor sulA, which dramatically enhanced the thickness and biomass of biofilm increased by 155% and 77%, respectively, is overexpressed. To reduce reaction overpotential due to biofilm thickness, a spider-web-like hybrid biofilm comprising RF, multiwalled carbon nanotubes (MWCNTs), and graphene oxide (GO) with adsorption-optimized elongated S. oneidensis, achieve a 77.83-fold increase in power (3736 mW m-2 ) relative to MR-1 and dramatically reduce the charge-transfer resistance and boosted biofilm electroactivity. This work provides an elegant paradigm to boost EET based on a synthetic biology strategy and materials science strategy, opens up further opportunities for other electrogenic bacteria.


Assuntos
Nanotubos de Carbono , Shewanella , Elétrons , Riboflavina/metabolismo , Shewanella/metabolismo , Biofilmes
12.
Sci Total Environ ; 866: 161346, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36603637

RESUMO

Phosphate addition is commonly applied to remediate lead contaminated sites via the formation of lead phosphate particles with low solubility. However, the effects of natural organic matter (NOM) with different properties, as well as the contributions of specific interactions (particle-particle, particle-NOM, and NOM-NOM) in enhanced stabilization or flocculation of the particles, are not currently well understood. This study investigates the influence of two aquatic NOM and two soil or coal humic acid (HA) extracts on the aggregation behavior of lead phosphate particles and explores the controlling mechanisms. All types of NOM induced disaggregation and steric stabilization of the particles in the presence of Na+ (100 mM) or low (1 mM) Ca2+ concentrations, as well as at low NOM concentrations (1 mgC/L). However, for the soil and coal HA, a threshold at NOM concentrations of 10 mgC/L and high (3 mM) Ca2+ concentrations was observed where bridging flocculation (rather than steric stabilization) occurred. In situ attenuated total reflectance - Fourier transform infrared characterization confirmed adsorption of the soil and coal humic acid extracts (10 mgC/L) onto the surface of the lead phosphate particles in 3 mM Ca2+, whereas dynamic and static light scattering demonstrated extensive HA flocculation that dominated the overall scattered light intensities. These results imply that the accelerated aggregation was induced by a combination of HA adsorption and bridging flocculation by Ca2+. Overall, this research demonstrates that the type of NOM is critical to predict the colloidal stability of lead phosphate particles. Aquatic NOM stabilized the particles under all conditions evaluated, but soil or coal HA with higher molecular weight and aromaticity showed highly variable stabilization or flocculation behavior depending on the HA and Ca2+ concentrations available to adsorb to the particles and participate in bridging. These results provide new mechanistic insights on particle stabilization or destabilization by NOM.

13.
Chemosphere ; 319: 137992, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36720411

RESUMO

The poor colloidal stability of magnetite nanoparticles (MNPs) limits their mobility and application, so various organic coatings (OCs) were applied to MNPs. Here, a comparative study on the colloidal stability of MNPs coated with acetic (HAc) and polyacrylic acids (PAA) was conducted under varied pH (5.0-9.0) in the presence of different concentrations of cations and anions, as well as humic acid (HA). Comparing the effects of various cations and anions, the stability of both HAc/PAA-MNPs followed the order: Na+ > Ca2+and PO43- > SO42- > Cl-, which could be explained by their adsorption behaviors onto HAc/PAA-MNPs and the resulting surface charge changes. Under all conditions even with more anion adsorption onto HAc-MNPs (0.14-22.56 mg/g) than onto PAA-MNPs (0.04-18.34 mg/g), PAA-MNPs were more negatively charged than HAc-MNPs, as PAA has a lower pHIEP (2.6 ± 0.1) than that of HAc (3.7 ± 0.1). Neither the HAc nor PAA coatings were displaced by phosphate even at considerably high phosphate concentration. Compared with HAc-MNPs, the stability of PAA-MNPs was greatly improved under all studied conditions, which could be due to both stronger electrostatic and additional steric repulsion forces among PAA-MNPs. Besides, under all conditions, Derjaguin-Landau-Verwey-Overbeek (DLVO) explained well the aggregation kinetic of HAc-MNPs; while extended DLVO (EDLVO) successfully predict that of PAA-MNPs, indicating steric forces among PAA-MNPs. The aggregation of HAc/PAA-MNPs was all inhibited in varied electrolyte solutions by HA (2 mg C/L) addition. This study suggested that carboxyl coatings with higher molecular weights and pKa values could stabilize MNPs better due to stronger electrostatic and additional steric repulsion. However, in the presence of HA, these two forces were mainly controlled by adsorbed HA instead of the organic pre-coatings on MNPs.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Substâncias Húmicas/análise , Nanopartículas de Magnetita/química , Eletrólitos/química , Cátions , Fosfatos , Concentração de Íons de Hidrogênio , Nanopartículas/química
14.
Front Cell Infect Microbiol ; 13: 1321094, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38239503

RESUMO

Introduction: Candida glabrata has emerged as a fungal pathogen with high infection and mortality rates, and its primary virulence factors are related to adhesion and biofilm formation. These virulence factors in C.glabrata are primarily mediated by epithelial adhesins (Epas), most of which are encoded in subtelomeric regions and regulated by subtelomeric silencing mechanisms. The transcription factor Mss11, known for its regulatory role in adhesion, biofilm formation, and filamentous growth in Saccharomyces cerevisiae and Candida albicans, has also been implicated in the expression of EPA6, suggesting its potential influence on C.glabrata virulence. The present study aims to determine the regulatory role of Mss11 in the virulence of C. glabrata. Methods: In this work, a Δmss11 null mutant and its complemented strain were constructed from a C.glabrata standard strain. The impact of the transcription factor Mss11 on the virulence of C.glabrata was investigated through a series of phenotypic experiments, including the microbial adhesion to hydrocarbons (MATH) test, adherence assay, biofilm assay, scanning electron microscopy and Galleria mellonella virulence assay. Furthermore, transcriptome sequencing, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation sequencing (ChIP-seq) were employed to investigate the molecular mechanisms behind the regulation of Mss11. Results: In C.glabrata, the loss of MSS11 led to a significant reduction in several virulence factors including cell surface hydrophobicity, epithelial cell adhesion, and biofilm formation. These observations were consistent with the decreased virulence of the Δmss11 mutant observed in the Galleria mellonella infection model. Further exploration demonstrated that Mss11 modulates C. glabrata virulence by regulating EPA1 and EPA6 expression. It binds to the upstream regions of EPA1 and EPA6, as well as the promoter regions of the subtelomeric silencing-related genes SIR4, RIF1, and RAP1, indicating the dual regulatory role of Mss11. Conclusion: Mss11 plays a crucial role in C. glabrata adhesion and biofilm formation, and thus has a broad influence on virulence. This regulation is achieved by regulating the expression of EPA1 and EPA6 through both promoter-specific regulation and subtelomeric silencing.


Assuntos
Candida glabrata , Proteínas de Saccharomyces cerevisiae , Candida glabrata/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Virulência/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Saccharomyces cerevisiae/metabolismo , Adesão Celular , Biofilmes , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Proteínas Repressoras/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Ligação a Telômeros/metabolismo
15.
J Colloid Interface Sci ; 641: 961-971, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36989822

RESUMO

Lanthanide (Ln3+) luminescent materials play a crucial role in information security and data storage owing to their excellent and unique optical properties. The advances in dynamic colorful luminescent anti-counterfeiting nanomaterials enable the generation of a high-level information encryption. In this work, a superior thermal, optical wavelength and excitation power triple-mode stimuli-responsive emission color modulation is demonstrated in a lanthanide-doped nanostructured luminescent material. The plentiful emission colors are manipulated by modulating the composition of a fluoride core-shell nanostructure with different Ln3+ at different doping concentrations. The nanomaterials display remarkable excitation wavelength/power-dependent color change, along with temperature-dependent color variation in the range from 298 K to 437 K, with a good relative sensitivity Sr of 1.1387% K-1 at 398 K. The universal optical modulation, combined with the excellent optical and structural stability of the luminescent nanoparticles, renders many advantages for the anti-counterfeiting application. This work explores a universal strategy for the manipulation of triple-mode stimuli-responsive dynamic luminescence and demonstrates its good potential for anti-counterfeiting application.

16.
Bioorg Med Chem Lett ; 22(10): 3554-9, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22507960

RESUMO

A series of novel methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamates were designed, synthesized, and their acrosin inhibitory activities evaluated in vitro. The results of acrosin inhibitory activity showed that all title compounds were more potent than the control TLCK. Compound 4w displayed the most potent acrosin inhibitory activity among all the compounds, with an IC(50) of 6.3×10(-5)M. The studies provide a new structural class for the development of novel acrosin inhibitory agents.


Assuntos
Acrosina/antagonistas & inibidores , Benzimidazóis/farmacologia , Benzimidazóis/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Moleculares
17.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 4): o1111, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22589968

RESUMO

The asymmetric unit of the title compound, C(12)H(12)N(2)O(3), contains two mol-ecules in which the benzene and isoxazole rings are almost coplanar, the dihedral angles between their mean planes being 1.76 (9) and 5.85 (8)°. The two mol-ecules inter-act with each other via N-H⋯N and N-H⋯O hydrogen bonds, which link the mol-ecules into layers parallel to the ac plane. The layers stack in a parallel mode with an inter-layer distance of 3.36 (7) Å.

18.
Sci Total Environ ; 831: 154976, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35378183

RESUMO

Magnetite nanoparticles (MNPs) with varied organic coatings (OCs) which improved their stability have broad environmental applications. However, the adsorbed amounts and layer thickness of varied OCs onto MNPs during the synthesis were generally not or poorly characterized, and their interactions with natural organic matter (NOM) were still in progress. In this study, acetic (HAc), citric (CA), and polyacrylic acid (PAA) were selected as model OCs, the adsorption behaviors of OCs on MNPs were characterized under varied aqueous C/Fe ratios, and the aggregation behaviors of MNPs with varied OCs (OC-MNPs) at neutral pH (7.0 ± 0.2) with NaCl (5-800 mM) in the presence/absence of NOM were systematically investigated. Under low aqueous C/Fe ratio, the adsorbed amounts of model OCs as -COOH/Fe ratio followed the order: CA ≈ PAA > > HAc. With high aqueous C/Fe ratio, the maximum adsorbed masses of OC-MNPs were similar. The adsorbed layer thicknesses of OC-MNPs were thoroughly characterized using three different methods, all showing that the adsorbed layer of PAA was thicker than that of CA and HAc. Derjaguin-Landau-Verwey-Overbeek (DLVO) and extended DLVO (EDLVO) calculations showed that electrostatic and van der Waals forces were dominant for CA-MNPs and HAc-MNPs stabilization; while steric repulsion played major roles in stabilizing PAA-MNPs, probably due to a thicker PAA layer. In the presence of NOM, stability behaviors of all OC-MNPs were similar, ascribing to the much greater amounts of NOM adsorbed than the OCs, causing greater steric repulsion. This study provides new mechanistic insights which could help better understand the effects of varied OCs on MNPs' colloidal stability.

19.
Water Res ; 214: 118200, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35228037

RESUMO

Phosphate addition is commonly applied as an effective method to remediate lead contaminated sites via formation of low solubility lead phosphate solids. However, subsequent transport of the lead phosphate particles may impact the effectiveness of this remediation strategy. Hence, this study investigates the mechanisms involved in the aggregation of lead phosphate particles and their deposition in sand columns as a function of typical water chemistry parameters. Clean bed filtration theory was evaluated to predict the particle deposition behavior, using Derjaguin-Landau-Verwey-Overbeek (DLVO) theory to estimate particle-substrate interactions. The observed particle deposition was not predictable from the primary energy barrier in clean bed filtration models, even in simple monovalent background electrolyte (NaNO3), because weak deposition in a secondary energy minimum prevailed even at low ionic strength, and ripening occurred at ionic strengths of 12.5 mM or higher. For aged (aggregated) suspensions, straining also occurred at 12.5 mM or higher. Aggregation and deposition were further enhanced at low total P/Pb ratios (i.e., P/Pb = 1) and in the presence of divalent cations, such as Ca2+ (≥ 0.2 mM), which resulted in less negative particle surface potentials and weaker electrostatic repulsion forces. However, the presence of 5 mg C/L of humic acid induced strong steric or electrosteric repulsion, which hindered particle aggregation and deposition even in the presence of Ca2+. This study demonstrates the importance of myriad mechanisms in lead phosphate deposition and provides useful information for controlling water chemistry in phosphate applications for lead remediation.

20.
Braz J Microbiol ; 53(2): 727-738, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35122657

RESUMO

BACKGROUND: The Candida glabrata does not develop into a pathogenic hiphal form; however, it has become the second most common pathogen of fungal infections in humans, partly because of its adhesion ability and virulence. OBJECTIVES: The present study aimed to determine whether Flo8, a transcription factor that plays an important role in the virulence and drug resistance in Candida albicans, has a similar role in C. glabrata. METHODS: We constructed FLO8 null strains of a C. glabrata standard strain and eight clinical strains from different sources, and a FLO8 complemented strain. Real-time quantitative PCR, biofilm formation assays, hydrophobicity tests, adhesion tests, Caenorhabditis elegans survival assay, and drug-susceptibility were then performed. RESULTS: Compared with the wild-type strains, the biofilm formation, hydrophobicity, adhesion, and virulence of the FLO8-deficient strains decreased, accompanied by decreased expression of EPA1, EPA6, and EPA7. On the other hand, it showed no changes in antifungal drug resistance, although the expression levels of CDR1, CDR2, and SNQ2 increased after FLO8 deletion. CONCLUSIONS: These results indicated that Flo8 is involved in the adhesion and virulence of C. glabrata, with FLO8 deletion leading to decreased expression of EPA1, EPA6, and EPA7 and decreased biofilm formation, hydrophobicity, adhesion, and virulence.


Assuntos
Candida glabrata , Proteínas Fúngicas , Antifúngicos/farmacologia , Biofilmes , Candida albicans/metabolismo , Candida glabrata/genética , Candida glabrata/metabolismo , Farmacorresistência Fúngica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Virulência
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