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1.
Langmuir ; 37(34): 10394-10401, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34403253

RESUMO

Fibrinogen (Fg) self-assembly is sensitive to the physicochemical properties of an environment like pH and ionic strength. These parameters tune the direction and strength of noncovalent physical driving forces determining protein intermolecular interactions. The attraction-repulsion balance in intermolecular interactions of the multidomain protein Fg at pH values 3.5, 7.4, and 9.5 and varying ionic strengths of the water medium has been analyzed by the complex diffusive approach, proposed by us previously. The concentration dependence of protein collective diffusion was analyzed within the phenomenological approach, based on the frictional formalism of nonequilibrium thermodynamics proposed by H. Vink. The analysis of protein diffusion data has shown the fundamental difference in the physical nature and direction of interaction forces between protein molecules at different conditions. The paired interaction potential of protein molecules was characterized in terms of second virial coefficients and Hamaker constants within the Deryaguin-Landau-Verwey-Overbeek theory and the "porous" colloid particle model. Our results indicated the maximum Hamaker constant and dominance of the van der Waals attraction between Fg molecules at pH 7.4. The increase in pH up to 9.5 results in the zero values of the second virial coefficient and Hamaker constant, corresponding to the full reciprocal compensation for electrostatic repulsion and van der Waals attraction. In the acidic medium (pH 3.5), the strong electrostatic repulsion substantially exceeds the van der Waals attraction. A high ionic strength is characterized by a significant decrease of all intermolecular interactions, which is expressed in almost zero values of virial coefficients and the Hamaker constant. Thus, it is experimentally shown that the physiological conditions of the Fg environment (pH 7.4 and slight ionic strength) provide a high probability for peak physical attraction between fibrinogen molecules, which is used in nature to facilitate blood clotting.


Assuntos
Fibrinogênio , Concentração de Íons de Hidrogênio , Concentração Osmolar , Eletricidade Estática , Termodinâmica
2.
Sensors (Basel) ; 21(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34451066

RESUMO

We show that an SnO2-based water-gate thin film transistor (WGTFT) biosensor responds to a waterborne analyte, the spike protein of the SARS-CoV-2 virus, by a parallel potentiometric and capacitive mechanism. We draw our conclusion from an analysis of transistor output characteristics, which avoids the known ambiguities of the common analysis based on transfer characteristics. Our findings contrast with reports on organic WGTFT biosensors claiming a purely capacitive response due to screening effects in high ionic strength electrolytes, but are consistent with prior work that clearly shows a potentiometric response even in strong electrolytes. We provide a detailed critique of prior WGTFT analysis and screening reasoning. Empirically, both potentiometric and capacitive responses can be modelled quantitatively by a Langmuir‒Freundlich (LF) law, which is mathematically equivalent to the Hill equation that is frequently used for biosensor response characteristics. However, potentiometric and capacitive model parameters disagree. Instead, the potentiometric response follows the Nikolsky-Eisenman law, treating the analyte 'RBD spike protein' as an ion carrying two elementary charges. These insights are uniquely possible thanks to the parallel presence of two response mechanisms, as well as their reliable delineation, as presented here.


Assuntos
Técnicas Biossensoriais , COVID-19 , Humanos , Concentração Osmolar , SARS-CoV-2 , Água
3.
FASEB J ; 35(9): e21778, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34383971

RESUMO

As a result of the relatively few available antifungals and the increasing frequency of resistance to them, the development of novel antifungals is increasingly important. The plant natural product poacic acid (PA) inhibits ß-1,3-glucan synthesis in Saccharomyces cerevisiae and has antifungal activity against a wide range of plant pathogens. However, the mode of action of PA is unclear. Here, we reveal that PA specifically binds to ß-1,3-glucan, its affinity for which is ~30-fold that for chitin. Besides its effect on ß-1,3-glucan synthase activity, PA inhibited the yeast glucan-elongating activity of Gas1 and Gas2 and the chitin-glucan transglycosylase activity of Crh1. Regarding the cellular response to PA, transcriptional co-regulation was mediated by parallel activation of the cell-wall integrity (CWI) and high-osmolarity glycerol signaling pathways. Despite targeting ß-1,3-glucan remodeling, the transcriptional profiles and regulatory circuits activated by caspofungin, zymolyase, and PA differed, indicating that their effects on CWI have different mechanisms. The effects of PA on the growth of yeast strains indicated that it has a mode of action distinct from that of echinocandins, suggesting it is a unique antifungal agent.


Assuntos
Antifúngicos/farmacologia , Parede Celular/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Glicerol/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Estilbenos/farmacologia , Transcrição Genética/efeitos dos fármacos , beta-Glucanas/farmacologia , Caspofungina/farmacologia , Parede Celular/genética , Parede Celular/metabolismo , Quitina/farmacologia , Equinocandinas/farmacologia , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/genética , Concentração Osmolar , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transcrição Genética/genética
4.
Nutrients ; 13(8)2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34444949

RESUMO

The prevalence of gastritis in humans is constantly growing and a prediction of an increase in this health problem is observed in many countries. For this reason, effective dietary therapies are sought that can alleviate the course of this disease. The objective of this study was to determine the effect of chemically pure oat beta-glucan preparations with different molar masses, low or high, used for 30 days in patients with histologically diagnosed chronic gastritis. The study enrolled 48 people of both genders of different ages recruited from 129 patients with a gastritis diagnosis. Before and after the therapy, hematological, biochemical, immunological and redox balance parameters were determined in the blood and the number of lactic acid bacteria and SCFA concentrations in the feces. Our results demonstrated a beneficial effect of oat beta-glucans with high molar mass in chronic gastritis in humans, resulting in reduced mucosal damage and healthy changes in SCFA fecal concentration and peripheral blood serum glutathione metabolism and antioxidant defense parameters. This fraction of a highly purified oat beta-glucan is safe for humans. Its action is effective after 30 days of use, which sheds new light on the nutritional treatment of chronic gastritis.


Assuntos
Avena , Gastrite/dietoterapia , beta-Glucanas/administração & dosagem , Adulto , Idoso , Doença Crônica , Método Duplo-Cego , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fezes/microbiologia , Feminino , Gastrite/microbiologia , Humanos , Lactobacillales/metabolismo , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Resultado do Tratamento , Adulto Jovem
5.
Biomaterials ; 276: 121035, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34303153

RESUMO

Virus-like particles (VLPs) holding internal cavity with diameter from tens up to one hundred nanometers are attractive platform for drug delivery. Nevertheless, the packing of drugs in the nanocage mainly relies on complicated disassembly-reassembly process. In this study, hepatitis B core protein (HBc) VLPs which can withstand temperature up to 90 °C was employed as carrier to load a lipophilic near infrared dye IR780. It was found that an attaching-dis-atching-diffusing process was involved for the entering of IR780 in the cavity of HBc. The first two steps were associated with the electrostatic interactions between oppositely charged HBc and IR780, which was critically manipulated by ionic strength and HBc/IR780 mass ratio at which they were mixed; while the diffusion of IR780 across the shell of HBc showed a temperature-dependent manner that can be triggered by thermal induced pore-opening of the HBc capsid. At optimized condition, about 1055 IR780 molecules were encapsulated in each HBc by simply mixing them for 10 min at 60 °C. Compared with free IR780, the HBc-IR780 particles showed significantly improved aqueous and photostability, as well as enhanced photothermal and photodynamic performance for cancer therapy. This study provides a novel drug loading strategy and nanomemedicine for cancer phototherapies.


Assuntos
Hepatite B , Neoplasias , Hepatite B/terapia , Humanos , Indóis , Concentração Osmolar , Fototerapia
6.
J Chem Phys ; 154(19): 195103, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34240890

RESUMO

Interactions among ions and their specific interactions with macromolecular solutes are known to play a central role in biomolecular stability. However, similar effects in the conformational stability of protein loops that play functional roles, such as binding ligands, proteins, and DNA/RNA molecules, remain relatively unexplored. A well-characterized enzyme that has such a functional loop is Escherichia coli dihydrofolate reductase (ecDHFR), whose so-called M20 loop has been observed in three ordered conformations in crystal structures. To explore how solution ionic strengths may affect the M20 loop conformation, we proposed a reaction coordinate that could quantitatively describe the loop conformation and used it to classify the loop conformations in representative ecDHFR x-ray structures crystallized in varying ionic strengths. The Protein Data Bank survey indicates that at ionic strengths (I) below the intracellular ion concentration-derived ionic strength in E. coli (I ≤ 0.237M), the ecDHFR M20 loop tends to adopt open/closed conformations, and rarely an occluded loop state, but when I is >0.237M, the loop tends to adopt closed/occluded conformations. Distance-dependent electrostatic potentials around the most mobile M20 loop region from molecular dynamics simulations of ecDHFR in equilibrated CaCl2 solutions of varying ionic strengths show that high ionic strengths (I = 0.75/1.5M) can preferentially stabilize the loop in closed/occluded conformations. These results nicely correlate with conformations derived from ecDHFR structures crystallized in varying ionic strengths. Altogether, our results suggest caution in linking M20 loop conformations derived from crystal structures solved at ionic strengths beyond that tolerated by E. coli to the ecDHFR function.


Assuntos
Cloreto de Cálcio/química , Escherichia coli/enzimologia , Tetra-Hidrofolato Desidrogenase/química , Simulação de Dinâmica Molecular , Concentração Osmolar , Conformação Proteica , Soluções , Tetra-Hidrofolato Desidrogenase/metabolismo
7.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298976

RESUMO

The voltage-dependent anion channel (VDAC) is the primary regulating pathway of water-soluble metabolites and ions across the mitochondrial outer membrane. When reconstituted into lipid membranes, VDAC responds to sufficiently large transmembrane potentials by transitioning to gated states in which ATP/ADP flux is reduced and calcium flux is increased. Two otherwise unrelated cytosolic proteins, tubulin, and α-synuclein (αSyn), dock with VDAC by a novel mechanism in which the transmembrane potential draws their disordered, polyanionic C-terminal domains into and through the VDAC channel, thus physically blocking the pore. For both tubulin and αSyn, the blocked state is observed at much lower transmembrane potentials than VDAC gated states, such that in the presence of these cytosolic docking proteins, VDAC's sensitivity to transmembrane potential is dramatically increased. Remarkably, the features of the VDAC gated states relevant for bioenergetics-reduced metabolite flux and increased calcium flux-are preserved in the blocked state induced by either docking protein. The ability of tubulin and αSyn to modulate mitochondrial potential and ATP production in vivo is now supported by many studies. The common physical origin of the interactions of both tubulin and αSyn with VDAC leads to a general model of a VDAC inhibitor, facilitates predictions of the effect of post-translational modifications of known inhibitors, and points the way toward the development of novel therapeutics targeting VDAC.


Assuntos
Ânions/metabolismo , Respiração Celular/fisiologia , Proteínas Intrinsicamente Desordenadas/fisiologia , Membranas Mitocondriais/efeitos dos fármacos , Tubulina (Proteína)/fisiologia , Canais de Ânion Dependentes de Voltagem/antagonistas & inibidores , alfa-Sinucleína/fisiologia , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , Respiração Celular/efeitos dos fármacos , Fluoresceínas/química , Humanos , Proteínas Intrinsicamente Desordenadas/química , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/fisiologia , Cinética , Membranas Mitocondriais/metabolismo , Modelos Moleculares , Concentração Osmolar , Cloreto de Potássio/farmacologia , Conformação Proteica , Mapeamento de Interação de Proteínas , Processamento de Proteína Pós-Traducional , Transporte Proteico , Alinhamento de Sequência , Ácidos Sulfônicos/química , Tubulina (Proteína)/química , Canais de Ânion Dependentes de Voltagem/química , Canais de Ânion Dependentes de Voltagem/fisiologia , alfa-Sinucleína/química
8.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298985

RESUMO

In this study, the temperature-dependent solubility of nicotinamide (niacin) was measured in six neat solvents and five aqueous-organic binary mixtures (methanol, 1,4-dioxane, acetonitrile, DMSO and DMF). It was discovered that the selected set of organic solvents offer all sorts of solvent effects, including co-solvent, synergistic, and anti-solvent features, enabling flexible tuning of niacin solubility. In addition, differential scanning calorimetry was used to characterize the fusion thermodynamics of nicotinamide. In particular, the heat capacity change upon melting was measured. The experimental data were interpreted by means of COSMO-RS-DARE (conductor-like screening model for realistic solvation-dimerization, aggregation, and reaction extension) for concentration dependent reactions. The solute-solute and solute-solvent intermolecular interactions were found to be significant in all of the studied systems, which was proven by the computed mutual affinity of the components at the saturated conditions. The values of the Gibbs free energies of pair formation were derived at an advanced level of theory (MP2), including corrections for electron correlation and zero point vibrational energy (ZPE). In all of the studied systems the self-association of nicotinamide was found to be a predominant intermolecular complex, irrespective of the temperature and composition of the binary system. The application of the COSMO-RS-DARE approach led to a perfect match between the computed and measured solubility data, by optimizing the parameter of intermolecular interactions.


Assuntos
Niacinamida/química , Termodinâmica , Acetonitrilas , Varredura Diferencial de Calorimetria , Cristalografia por Raios X , Dimerização , Dimetil Sulfóxido , Dimetilformamida , Dioxanos , Metanol , Modelos Químicos , Concentração Osmolar , Solubilidade , Soluções , Solventes , Espectrofotometria Infravermelho , Temperatura , Vibração , Água
9.
Nutrients ; 13(6)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199607

RESUMO

BACKGROUND: The consumption of sweetened beverages is associated with increased risk of metabolic syndrome, cardiovascular disease, and type 2 diabetes mellitus. OBJECTIVE: We hypothesized that the metabolic effects of fructose in sugary beverages might be modulated by the speed of ingestion in addition to the overall amount. DESIGN: Thirty healthy subjects free of any disease and medication were recruited into two groups. After overnight fasting, subjects in group 1 drank 500 mL of apple juice over an hour by drinking 125 mL every 15 min, while subjects in group 2 drank 500 mL of apple juice over 5 min. Blood samples were collected at time zero and 15, 30, 60, and 120 min after ingestion to be analyzed for serum glucose, insulin, homeostatic model assessment (HOMA-IR) score, fibroblast growth factor 21, copeptin, osmolarity, sodium, blood urea nitrogen (BUN), lactate, uric acid, and phosphate levels. RESULTS: Serum glucose, insulin, HOMA-IR, fibroblast growth factor 21, copeptin, osmolarity, sodium, BUN, and lactate levels increased following apple juice ingestion. The increases were greater in the fast-drinking group, which were more significant after 15 min and 30 min compared to baseline. The changes in uric acid were not statistically different between the groups. Phosphate levels significantly increased only in the fast-drinking group. CONCLUSION: Fast ingestion of 100% apple juice causes a significantly greater metabolic response, which may be associated with negative long-term outcomes. Our findings suggest that the rate of ingestion must be considered when evaluating the metabolic impacts of sweetened beverage consumption.


Assuntos
Ingestão de Alimentos , Frutose/efeitos adversos , Síndrome Metabólica/etiologia , Bebidas Adoçadas com Açúcar/efeitos adversos , Açúcares/efeitos adversos , Adulto , Glicemia , Diabetes Mellitus Tipo 2/complicações , Feminino , Fatores de Crescimento de Fibroblastos , Sucos de Frutas e Vegetais , Glucose , Glicopeptídeos , Humanos , Insulina , Masculino , Malus , Concentração Osmolar , Precursores de Proteínas/metabolismo , Ácido Úrico/sangue , Adulto Jovem
10.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206313

RESUMO

Recent trends in the food industry combined with novel methods in agriculture could transform rowan into a valuable raw material with potential technological applications. Thus, the aim of this research was to investigate the content of bioactive compounds in its fruits and to assess the color and antioxidant stability of the extracts prepared from such fruits during various thermal treatments and at different pH and ionic strength values. Various spectrophotometric methods, HPLC, and capillary electrophoresis were used to quantify the concentrations of bioactive compounds-polyphenols, carotenoids, organic acids, and to assess antioxidant activity and color. The results show that rowan berries contain circa 1.34-1.47 g/100 g of polyphenols among which include catechin, epicatechin, ferulic acid methyl ester, procyanidin B1, etc.; ca 21.65 mg/100 g of carotenoids including zeaxanthin, ß-cryptoxanthin, all-trans-ß-carotene, and various organic acids such as malic, citric, and succinic, which result in a high antioxidant activity of 5.8 mmol TE/100 g. Results also showed that antioxidant activity exhibited high stability when the extract was subjected to various thermal treatments, pHs, and ionic strengths, while color was mainly impacted negatively when a temperature of 100 °C was employed. This data confirms the technological potential of this traditional, yet often overlooked species.


Assuntos
Antioxidantes/química , Frutas/química , Pigmentos Biológicos/química , Extratos Vegetais/química , Sorbus/química , Concentração de Íons de Hidrogênio , Concentração Osmolar , Polifenóis/química
11.
Se Pu ; 39(4): 391-398, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-34227759

RESUMO

Urine is an important source of biomolecular information for metabolomic studies. However, the acquisition of high-quality metabolomic datasets or reliable biomarkers from urine is difficult owing to the large variations in the concentrations of endogenous metabolites in the biofluid, which are caused by diverse factors such as water consumption, drugs, and diseases. Thus, normalization or calibration is essential in urine metabolomics for eliminating such deviations. The urine osmolality (Π), which is a direct measure of the total urinary solute concentration and is not affected by circadian rhythms, diet, gender, and age, is often considered the gold standard for estimation of the urine concentration. In this study, a pre-data acquisition calibration strategy based on osmolality was investigated for its feasibility to overcome sample concentration variability. Before data acquisition, the product of the osmolality×injection volume of all samples was set to be equivalent through the uses of a customized injection volume or dilution. After ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) analysis of the sample, the raw dataset was normalized to the total ion abundance or total useful MS signals (MSTUS) to achieve further calibration. The osmolality of each urine sample was determined with a freezing-point depression osmometer. For the instrumental analysis, a Vanquish UPLC system coupled to a Q-Exactive Plus HRMS device was used for metabolite analysis and accurate mass measurement. Full-scan mass spectra were acquired in the range of m/z 60-900, and the MS/MS experiments were conducted in "Top5" data-dependent mode. A Waters UPLC column (100 mm×2.1 mm, 1.8 µm) was used for chromatography separation. The raw data were imported into Progenesis QI software for peak picking, alignment, deconvolution, and normalization. SIMCA-P software was used for the principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA). This strategy was first applied to sequentially diluted urine samples, where three frequently used normalization methods were compared. In the identical injection volume experiment, the points were scattered and showed relevant distribution according to the dilution multiple in the plot of PCA scores. There was little improvement after normalization to either the total ion abundance or MSTUS. In the customized injection volume experiment, the urine samples derived from the same source showed ideal clustering. With total ion abundance and MSTUS normalization, the dataset was further improved in the PCA model fitting and prediction. As a result, there were more peaks with a peak area RSD of <30%, which indicated better parallelism. The diluted urine solutions had higher Spearman's coefficient values with their sample source than those without calibration, which suggested less intra-group differences. The strategy was further validated using data from a metabolomic study of children with congenital hydronephrosis and healthy controls. As a concentration estimator, osmolality showed better linear correlation with the mass signal and was less influenced by physiological or pathological factors, thus obtaining broader application and more accurate results than creatinine. The concentration variability was effectively eliminated after customized dilution calibration and showed a more obvious clustering effect in the PCA score plot. The OPLS-DA-based statistical model used to identify discriminate metabolites was improved, with less chance of overfitting. In conclusion, the calibration strategy based on osmolality combined with total ion abundance or MSTUS normalization significantly overcame the problem of urine concentration variability, eliminated intra-group differences, and possessed better parallelism, thus giving better clustering effects in PCA or OPLS-DA and higher reliability of the statistical model. The results of this study provide guidance and a reference for future metabolomic studies on urine.


Assuntos
Hidronefrose/urina , Metabolômica , Urinálise , Calibragem , Criança , Cromatografia Líquida de Alta Pressão , Humanos , Hidronefrose/congênito , Concentração Osmolar , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
12.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201004

RESUMO

Cadmium is a carcinogen that can induce ER stress, DNA damage, oxidative stress and cell death. The yeast mitogen-activated protein kinase (MAPK) signalling pathways paly crucial roles in response to various stresses. Here, we demonstrate that the unfolded protein response (UPR) pathway, the high osmolarity glycerol (HOG) pathway and the cell wall integrity (CWI) pathway are all essential for yeast cells to defend against the cadmium-induced toxicity, including the elevated ROS and cell death levels induced by cadmium. We show that the UPR pathway is required for the cadmium-induced phosphorylation of HOG_MAPK Hog1 but not for CWI_MAPK Slt2, while Slt2 but not Hog1 is required for the activation of the UPR pathway through the transcription factors of Swi6 and Rlm1. Moreover, deletion of HAC1 and IRE1 could promote the nuclear accumulation of Hog1, and increase the cytosolic and bud neck localisation of Slt2, indicating crucial roles of Hog1 and Slt2 in regulating the cellular process in the absence of UPR pathway. Altogether, our findings highlight the significance of these two MAPK pathways of HOG and CWI and their interrelationship with the UPR pathway in responding to cadmium-induced toxicity in budding yeast.


Assuntos
Cádmio/toxicidade , Parede Celular/química , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Glicerol/farmacologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Parede Celular/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Concentração Osmolar , Fosforilação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Transdução de Sinais
13.
Nat Commun ; 12(1): 3741, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145296

RESUMO

Despite technological advances in biomolecule detections, evaluation of molecular interactions via potentiometric devices under ion-enriched solutions has remained a long-standing problem. To avoid severe performance degradation of bioelectronics by ionic screening effects, we cover probe surfaces of field effect transistors with a single film of the supported lipid bilayer, and realize respectable potentiometric signals from receptor-ligand bindings irrespective of ionic strength of bulky solutions by placing an ion-free water layer underneath the supported lipid bilayer. High-energy X-ray reflectometry together with the circuit analysis and molecular dynamics simulation discovered biochemical findings that effective electrical signals dominantly originated from the sub-nanoscale conformational change of lipids in the course of receptor-ligand bindings. Beyond thorough analysis on the underlying mechanism at the molecular level, the proposed supported lipid bilayer-field effect transistor platform ensures the world-record level of sensitivity in molecular detection with excellent reproducibility regardless of molecular charges and environmental ionic conditions.


Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Bicamadas Lipídicas/química , Potenciometria/instrumentação , Potenciometria/métodos , Membrana Celular/metabolismo , Lipídeos de Membrana/metabolismo , Simulação de Dinâmica Molecular , Concentração Osmolar , Transistores Eletrônicos
14.
Yonsei Med J ; 62(7): 600-607, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34164957

RESUMO

PURPOSE: Plasma osmolality, a marker of dehydration, is associated with cardiovascular mortality. We aimed to investigate whether elevated plasma osmolality is associated with case fatality within 1 year after severe acute ischemic stroke. MATERIALS AND METHODS: We included severe ischemic stroke patients (defined as National Institutes of Health Stroke Scale ≥15 score) within 24 hours from symptom onset admitted to the Department of Neurology, West China Hospital between January 2017 and June 2019. Admission plasma osmolality was calculated using the equation 1.86*(sodium+potassium)+1.15*glucose+urea+14. Elevated plasma osmolality was defined as plasma osmolality >296 mOsm/kg, indicating a state of dehydration. Study outcomes included 3-month and 1-year case fatalities. Multivariable logistic regression was performed to determine independent associations between plasma osmolality and case fatalities at different time points. RESULTS: A total of 265 patients with severe acute ischemic stroke were included. The mean age was 71.2±13.1 years, with 51.3% being males. Among the included patients, case fatalities were recorded for 31.7% (84/265) at 3 months and 39.6% (105/265) at 1 year. Elevated plasma osmolality (dehydration) was associated with 3-month case fatality [odds ratio (OR) 1.98, 95% confidence interval (CI) 1.07-3.66, p=0.029], but not 1-year case fatality (OR 1.51, 95% CI 0.84-2.72, p=0.165), after full adjustment for confounding factors. CONCLUSION: Elevated plasma osmolality was independently associated with 3-month case fatality, but not 1-year case fatality, for severe acute ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Fatores de Risco
15.
Nutrients ; 13(6)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064102

RESUMO

Euhydration remains a challenge in children due to lack of access and unpalatability of water and to other reasons. The purpose of this study was to determine if the availability/access to a beverage (Creative Roots®) influences hydration in children and, therefore, sleep quality and mood. Using a crossover investigation, 46 participants were randomly assigned to a control group (CON) or an intervention group and received Creative Roots® (INT) for two-week periods. We recorded daily first morning and afternoon urine color (Ucol), thirst perception, and bodyweight of the two groups. Participants reported to the lab once per week and provided first morning urine samples to assess Ucol, urine specific gravity (USG), and urine osmolality (Uosmo). Participants also completed the questionnaires Profile of Mood States-Adolescents (POMS-a) and Pittsburgh Sleep Quality Index (PSQI). Dependent t-tests were used to assess the effects of the intervention on hydration, mood, and sleep quality. Uosmo was greater and Ucol was darker in the control group (mean ± SD) [Uosmo: INT = 828 ± 177 mOsm·kg-1, CON = 879 ± 184 mOsm·kg-1, (p = 0.037], [Ucol:INT = 5 ± 1, CON = 5 ± 1, p = 0.024]. USG, POMS-a, and PSQI were not significant between the groups. At-home daily afternoon Ucol was darker in the control group [INT = 3 ± 1, CON = 3 ± 1, p = 0.022]. Access to Creative Roots® provides a small, potentially meaningful hydration benefit in children. However, children still demonstrated consistent mild dehydration based on Uosmo, despite consuming the beverage.


Assuntos
Afeto/fisiologia , Bebidas/provisão & distribuição , Desidratação/urina , Comportamento de Ingestão de Líquido/fisiologia , Aromatizantes/administração & dosagem , Sono/fisiologia , Peso Corporal , Criança , Estudos Cross-Over , Desidratação/etiologia , Feminino , Humanos , Masculino , Concentração Osmolar , Gravidade Específica , Sede/fisiologia
16.
Nat Struct Mol Biol ; 28(6): 465-473, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34099940

RESUMO

Biomolecular condensates that form via phase separation are increasingly regarded as coordinators of cellular reactions that regulate a wide variety of biological phenomena. Mounting evidence suggests that multiple steps of the RNA life cycle are organized within RNA-binding protein-rich condensates. In this Review, we discuss recent insights into the influence of phase separation on RNA biology, which has implications for basic cell biology, the pathogenesis of human diseases and the development of novel therapies.


Assuntos
Proteínas de Ligação a RNA/química , RNA/química , Ribonucleoproteínas/química , Animais , Núcleo Celular/química , Núcleo Celular/fisiologia , Citoplasma/química , Citoplasma/fisiologia , Humanos , Proteínas Intrinsicamente Desordenadas/química , Mamíferos/metabolismo , Proteínas de Neoplasias/química , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Concentração Osmolar , Transição de Fase , Agregação Patológica de Proteínas/prevenção & controle , Conformação Proteica , Domínios Proteicos , Isoformas de Proteínas/química , Processamento de Proteína Pós-Traducional , RNA/metabolismo , Splicing de RNA , RNA Neoplásico/metabolismo , Relação Estrutura-Atividade
17.
Environ Res ; 200: 111451, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34102160

RESUMO

The transport and retention of two-dimensional (2D) nanomaterials, such as graphene oxide, in porous media have attracted lots of attention. However, previous studies often simplified these 2D colloids as equivalent spheres for numerical simulations, which ignored the influence of particle shape on colloid retention at multiple interfaces. In this study, a novel 2D nanomaterial delaminated Ti3C2Tx (d-Ti3C2Tx) was adopted to fill this knowledge gap. Comprehensive analyses of the 2D colloid retention mechanisms were conducted based on colloid characterization, saturated and unsaturated column experiments, reactive transport modeling, 2D-based DLVO and nonspherical capillary energy simulations. Results show that d-Ti3C2Tx mobility in both saturated and unsaturated conditions enhanced with the increase in pH and decrease in ionic strength. The DLVO interaction energy of d-Ti3C2Tx at the sand-water-interface (SWI) decreased with the orientation angle of the colloidal major axis to the sand surface from 0° to 90°. The primary mechanism under saturated flow conditions was the irreversible attachment in the deep secondary minimum at the SWI with the major axis of d-Ti3C2Tx parallel to the sand surface. The attachment in the primary minimum at 0° was impossible due to the extremely high energy barrier, and the attachment in the primary and secondary minimum at other orientation angles were negligible. d-Ti3C2Tx only experienced repulsive electrostatic force when approaching the air-water-interface (AWI) no matter the particle orientation. The detaching capillary potential energy was 3 orders of magnitude larger than the attractive DLVO interaction energy of the SWI in the secondary minimum at 0°, suggesting that the capillary force-induced irreversible attachment at the AWI was the primary mechanism under unsaturated flow conditions. This study shows that the DLVO and capillary potential energies were significantly dependent on the particle-interface orientation and colloidal shape. A simplification of 2D colloids as spheres is not recommended.


Assuntos
Coloides , Titânio , Cinética , Concentração Osmolar , Porosidade
18.
Int J Biol Macromol ; 182: 1852-1862, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062156

RESUMO

In the current work, the binding interaction of cabozantinib with salmon sperm DNA (SS-DNA) was studied under simulated physiological conditions (pH 7.4) using fluorescence emission spectroscopy, UV-Vis absorption spectroscopy, viscosity measurement, ionic strength measurement, FT-IR spectroscopy, and molecular modeling methods. The obtained experimental data demonstrated an apparent binding interaction of cabozantinib with SS-DNA. The binding constant (Kb) of cabozantinib with SS-DNA evaluated from the Benesi-Hildebrand plot was equal to 5.79 × 105 at 298 K. The entropy and enthalpy changes (∆S0 and ∆H0) in the binding interaction of SS-DNA with cabozantinib were 44.13 J mol-1 K-1 and -19.72 KJ mol-1, respectively, demonstrating that the basic binding interaction forces are hydrophobic and hydrogen bonding interactions. Results from UV-Vis absorption spectroscopy, competitive binding interaction with rhodamine B or ethidium bromide, and viscosity measurements revealed that cabozantinib binds to SS-DNA via minor groove binding. The molecular docking results revealed that cabozantinib fits into the AT-rich region of the B-DNA minor groove and the binding site of cabozantinib was 4 base pairs long. Moreover, cabozantinib has eight active torsions, implying a high degree of flexibility in its structure, which played a significant role in the formation of a stable cabozantinib-DNA complex.


Assuntos
Anilidas/metabolismo , DNA/metabolismo , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/metabolismo , Piridinas/metabolismo , Salmão/metabolismo , Análise Espectral , Espermatozoides/metabolismo , Anilidas/química , Animais , DNA/química , Ligação de Hidrogênio , Cinética , Masculino , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Concentração Osmolar , Inibidores de Proteínas Quinases/química , Piridinas/química , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Viscosidade
19.
J Chromatogr A ; 1651: 462286, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34090056

RESUMO

The widespread use of quinolones has become an increasing global public health threat. In this study, IRMOF-3 coated SiO2/Fe3O4 were prepared via a facile room-temperature method. The prepared IRMOF-3 coated SiO2/Fe3O4 was used as a sorbent for magnetic solid phase extraction, and then combined with high-performance liquid chromatography-tandem mass spectrometry for the determination of 10 quinolines. The extraction conditions of magnetic solid phase extraction were studied in detail, and the optimal conditions were established. Under the optimal experimental conditions, the limits of quantification of 10 quinolones were in the range of 0.005-0.01 µg L-1, the relative standard deviations were 6.58-10.6% (n=7), the enrichment factors were 21.0-23.8 for water samples. The limits of quantification of 10 quinolones were in the range of 0.10-0.20 µg kg-1, the relative standard deviations were 5.95-14.5% (n=7), the enrichment factors were 1.08-1.24 for fish samples. The proposed method was applied for the determination of 10 quinolones in river water, aquacultural water and a fish sample, and enrofloxacin and ciprofloxacin were found in the fish sample.


Assuntos
Monitoramento Ambiental , Peixes/metabolismo , Fenômenos Magnéticos , Estruturas Metalorgânicas/química , Quinolonas/análise , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem , Poluentes Químicos da Água/análise , Adsorção , Animais , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Concentração Osmolar , Reprodutibilidade dos Testes , Dióxido de Silício/química
20.
J Chromatogr A ; 1651: 462297, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34111676

RESUMO

While current trends in Green Analytical Chemistry aim at reducing or simplifying sample treatment, food usually comprises complex matrices where direct analysis is not possible in most cases. In this context, sample treatment plays a pivotal role. Biogenic amines are naturally formed in many foodstuffs due to the action of microorganisms, while their presence has been associated with adverse health effects. In this work, the extraction of seven biogenic amines (cadaverine, histamine, phenylethylamine, putrescine, spermidine, spermine, and tyramine) from beer samples has been simplified using laboratory filter paper as sorbent without any further modification. The analysis of the eluates by direct infusion mass spectrometry reduces the time of analysis, increasing the sample throughput. This simple but effective method enabled the determination of the analytes with limits of detection as low as 0.06 mg L-1 and relative standard deviations better than 11.9%. The suitability of the method has been assessed by analyzing eight different types of beers by the standard addition method.


Assuntos
Cerveja/análise , Aminas Biogênicas/isolamento & purificação , Celulose/química , Filtração , Adsorção , Aminas Biogênicas/química , Calibragem , Concentração de Íons de Hidrogênio , Concentração Osmolar , Papel , Padrões de Referência , Espectrometria de Massas em Tandem/métodos
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