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BACKGROUND: Hydrogen peroxide (H2O2) plays a vital role in human health and have been regarded as a crucial analyte in metabolic processes, redox transformations, foods research and medical fields. Especially, the long-time and excessive digestion of H2O2 may even cause severe diseases. Although conventional instrumental methods and nanozymes-based colorimetric methods have been developed to accomplish the quantitative analysis of H2O2, the drawbacks of instrument dependence, cost-effectiveness, short lifespan, non-portable and unsustainable detection efficacies will limit their applications in different detection scenarios. RESULTS: Herein, to address these challenges, we have proposed a novel strategy for nanozyme (RuO2) hydrogel preparation by the solid support from cross-linked polyvinyl alcohol (PVA) and chitosan (CS) to both inherit the dominant peroxidase-like (POD) activity and protect the RuO2 from losing efficacies. Taking advantages from the hydrogel, the encapsulated RuO2 were further prepared as the regularly spherical beads (PCRO) to exhibit the sustainable, recyclable, and robust catalysis. Moreover, the intrinsic color interferences which originated from RuO2 can be avoided by the encapsulation strategy to promote the detection accuracy. Meanwhile, the high mechanical strength of PCRO shows the high stability, reproducibility, and cyclic catalysis to achieve the recyclable detection performance and long lifetime storage (40 days), which enables the sensitively detection of H2O2 with the detection limit as lower to 15 µM and the wide detection linear range from 0.025 to 1.0 mM. SIGNIFICANCE: On the basis of the unique properties, PCRO has been further adopted to construct a smartphone detection platform to realize the instrument-free and visual analysis of H2O2 in multi-types of milk and real water samples through capturing, processing, and analyzing the RGB values from the colorimetric photographs. Therefore, PCRO with the advanced detection efficacies holds the great potential in achieving the portable and on-site analysis of targets-of-interest.
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Quitosano , Hidrogeles , Peróxido de Hidrógeno , Alcohol Polivinílico , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Quitosano/química , Alcohol Polivinílico/química , Catálisis , Hidrogeles/química , Colorimetría , Límite de DetecciónRESUMEN
The prevention and control of natural gas hydrates is an important link in ensuring winter production. Traditional thermodynamic inhibitors, like methanol, are commonly utilized due to their low unit costs and pricing, but they come with considerable safety issues when used on-site due to their high toxicity, flammability, and explosive potential. A cost-effective and eco-friendly hydrate inhibitor was created by combining light polyol amine with other ingredients to solve this problem. At a concentration of 30%, the product has a flash point greater than 80°C and a solidification point of -45°C. With success rates of 99% and 100%, respectively, it was used for winter casing pre-injection anti-freezing operations and balancing tank defoamer anti-freezing operations. Experiments have demonstrated the effectiveness of this inhibitor in preventing the formation of natural gas hydrates. In wintertime on-site anti-freezing activities, the projected cost can be substituted for methanol, as it is essentially equivalent to methanol.
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Gas Natural , Agua/química , Estaciones del Año , TermodinámicaRESUMEN
Venezuelan equine encephalitis virus (VEEV) is a highly virulent pathogen whose nuclear localization signal (NLS) sequence from capsid protein binds to the host importin-α transport protein and blocks nuclear import. We studied the molecular mechanisms by which two small ligands, termed I1 and I2, interfere with the binding of VEEV's NLS peptide to importin-α protein. To this end, we performed all-atom replica exchange molecular dynamics simulations probing the competitive binding of the VEEV coreNLS peptide and I1 or I2 ligand to the importin-α major NLS binding site. As a reference, we used our previous simulations, which examined noncompetitive binding of the coreNLS peptide or the inhibitors to importin-α. We found that both inhibitors completely abrogate the native binding of the coreNLS peptide, forcing it to adopt a manifold of nonnative loosely bound poses within the importin-α major NLS binding site. Both inhibitors primarily destabilize the native coreNLS binding by masking its amino acids rather than competing with it for binding to importin-α. Because I2, in contrast to I1, binds off-site localizing on the edge of the major NLS binding site, it inhibits fewer coreNLS native binding interactions than I1. Structural analysis is supported by computations of the free energies of the coreNLS peptide binding to importin-α with or without competition from the inhibitors. Specifically, both inhibitors reduce the free energy gain from coreNLS binding, with I1 causing significantly larger loss than I2. To test our simulations, we performed AlphaScreen experiments measuring IC50 values for both inhibitors. Consistent with in silico results, the IC50 value for I1 was found to be lower than that for I2. We hypothesize that the inhibitory action of I1 and I2 ligands might be specific to the NLS from VEEV's capsid protein.
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Unión Competitiva , Simulación de Dinámica Molecular , Señales de Localización Nuclear , alfa Carioferinas , alfa Carioferinas/metabolismo , alfa Carioferinas/química , alfa Carioferinas/antagonistas & inhibidores , Ligandos , Señales de Localización Nuclear/química , Virus de la Encefalitis Equina Venezolana/metabolismo , Virus de la Encefalitis Equina Venezolana/química , Unión Proteica , Péptidos/química , Péptidos/metabolismo , Péptidos/farmacología , Secuencia de AminoácidosRESUMEN
Hepatitis B virus (HBV) acts as a severe public health threat, causing chronic liver diseases. Although the quantified evaluation of HBV infection can be obtained by estimating the capacity of the HBV DNA genome, it still lacks an effective and robust detection method without using enzymes or chemical labeling. Herein, we have designed a binary split fluorescent DNA aptasensor (bsFDA) by rationally splitting the lettuce aptamer into two functional DNA short chains and utilizing the HBV DNA segment complementary sequences (HDs). In this strategy, the bsFDA has been investigated to specifically recognize the HDs, forming a triplex DNA with the lettuce aptamer structure. Meanwhile, the turn-on fluorescence of bsFDA is obtained upon formation of a fluorescent complex between DFHO and the triplex DNA structure, allowing the enzyme-free, label-free, fast-responsive, and reliable fluorescence readout for detecting HDs and the potential HDs mutants. Moreover, bsFDA has been applied for spiked HDs analysis in different real matrixes, including human serum and cell lysate. The satisfactory recovery rates and reproducibility of the bsFDA reveal its potential detection efficacy for HDs analysis in biological samples. Overall, bsFDA holds great potential in developing functionalized aptasensors and realizing viral genome analysis in biological research.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , ADN Viral , Virus de la Hepatitis B , Lactuca , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , ADN Viral/análisis , Humanos , Lactuca/virología , Lactuca/química , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Límite de Detección , Hepatitis B/diagnóstico , Hepatitis B/sangre , Reproducibilidad de los ResultadosRESUMEN
Background: Elevated preoperative γ-glutamyl transferase (GGT) levels or reduced serum albumin levels have been established as negative prognostic factors for patients with hepatocellular carcinoma (HCC) and various other tumors. Nonetheless, the prognostic significance of the GGT to serum albumin ratio (GAR) in liver transplantation (LT) therapy for HCC is still not well-defined. Methods: A retrospective analysis was conducted on the clinical data of 141 HCC patients who underwent LT at Shulan (Hangzhou) Hospital from June 2017 to November 2020. Using the receiver operating characteristic (ROC) curve, the optimal GAR cutoff value to predict outcomes following LT was assessed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent risk factors associated with both overall survival (OS) and recurrence-free survival (RFS). Results: A GAR value of 2.04 was identified as the optimal cutoff for predicting both OS and RFS, with a sensitivity of 63.2% and a specificity of 74.8%. Among these patients, 80 (56.7%) and 90 (63.8%) met the Milan and the University of California San Francisco (UCSF) criteria, respectively. Univariate Cox regression analysis showed that microvascular invasion (MVI), maximum tumor size (>5 cm), total tumor size (>8 cm), liver cirrhosis, TNM stage (III), and GAR (≥2.04) were significantly associated with both postoperative OS and RFS in patients with HCC (all p < 0.05). Multivariate Cox regression analysis indicated that GAR (≥2.04) was independently linked with RFS and OS. Conclusion: Pre-transplant GAR ≥2.04 is an independent correlate of prognosis and survival outcomes after LT for HCC and can be used as a prognostic indicator for both mortality and tumor recurrence following LT.
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2,5-bis(hydroxymethyl)furan (BHMF) derived from 5-Hydroxymethylfurfural (HMF) through a hydrogenation process has extensive applications in the production of resins, polymers, and artificial fibers. However, screening out the candidate and then modulating the active site to optimize the catalyst for high yield of BHMF are currently insufficient. In this study, Gibbs free energy diagrams of the reduction of HMF on 13 metals were presented, along with the identification of the rate-determining step (RDS) with the highest reaction barrier for each metal. We attempted to construct a volcano plot for HMFRR reaction. Additionally, a strategy was proposed to adjust the reaction barriers of RDS by combining two appropriate metals. Further experiments confirmed that Pb with the lowest energy barrier exhibited the highest HMF conversion (BHMF selectivity) among single metals. The modified catalyst by doping Ag on Pb, further boosted the HMF conversion (BHMF selectivity) from 42.1 % (59.4 %) to 80.8 % (80.9 %), respectively. These results provide an approach to rationally design and construct the catalyst system for efficient conversion of HMF.
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OBJECTIVE: This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. METHODS: The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). RESULTS: A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients' prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). CONCLUSIONS: Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.
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BACKGROUND: Organophosphorus pesticides (OPs) play important roles in the natural environment, agricultural fields, and biological prevention. The development of OPs detection has gradually become an effective strategy to avoid the dangers of pesticides abuse and solve the severe environmental and health problems in humans. Although conventional assays for OPs analysis such as the bulky instrument required analytical methods have been well-developed, it still remains the limitation of inconvenient, inefficient and lab-dependence analysis in real samples. Hence, there is an urgent demand to develop efficient detection methods for OPs analysis in real scenarios. RESULTS: Here, by virtue of the highly efficient catalytic performance in Fe7S8 nanoflakes (Fe7S8 NFs), we propose an OPs detection method that rationally integrated Fe7S8 NFs into the acetylcholine (ACh) triggered enzymatic cascade reaction (ATECR) for proceeding better detection performances. In this method, OPs serve as the enzyme inhibitors for inhibiting ATECR among ACh, acetylcholinesterase (AChE), and choline oxidase (CHO), then reduce the generation of H2O2 to suppress the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) that catalyzed by Fe7S8 NFs. Benefiting from the integration of Fe7S8 NFs and ATECR, it enables a sensitive detection for OPs (e.g. dimethoate). The proposed method has presented good linear ranges of OPs detection ranging from 0.1 to 10 µg mL-1. Compared to the other methods, the comparable limits of detection (LOD) of OPs are as low as 0.05 µg mL-1. SIGNIFICANCE: Furthermore, the proposed method has also achieved a favorable visual detection performance of revealing OPs analysis in real samples. The visual signals of OPs can be transformed into RGB values and gathered by using smartphones, indicating the great potential in simple, sensitive, instrument-free and on-site analysis of pesticide residues in environmental monitoring and biosecurity research.
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Técnicas Biosensibles , Plaguicidas , Piperidinas , Humanos , Plaguicidas/análisis , Acetilcolina/química , Acetilcolinesterasa/química , Compuestos Organofosforados/análisis , Peróxido de Hidrógeno/química , Catálisis , Técnicas Biosensibles/métodosRESUMEN
Neutral nanomaterials functionalized with PEG or similar molecules have been popularly employed as nanomedicines. Compared to positive counterparts that are capable of harnessing the well-known proton sponge effect to facilitate their escape from lysosomes, it is yet unclear how neutral substances got their entry into the cytosol. In this study, by taking PEGylated, neutral Au nanospheres as an example, we systematically investigated their time-dependent translocation postuptake. Specifically, we harnessed dissipative particle dynamics simulations to uncover how nanospheres bypass lysosomal entrapment, wherein a mechanism termed as "squeezing-out" mode was discovered. We next conducted a comprehensive investigation on how nanomaterials implicate lysosomes in terms of integrity and functionality. By using single-molecule imaging, specific preservation of PEG-terminated with targeting moieties in lysosomes supports the "squeezing-out" mode as the mechanism underlying the lysosomal escape of nanomaterials. All evidence points out that such a process is benign to lysosomes, wherein the escape of nanomaterials proceeds at the expense of targeting moieties loss. Furthermore, we proved that by fine-tuning of the efficacy of nanomaterials escaping from lysosomes, modulation of distinct pathways and metabolic machinery can be achieved readily, thereby offering us a simple and robust tool to implicate cells.
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Nanopartículas , Nanoestructuras , Ligandos , Separación de Fases , Lisosomas/metabolismoRESUMEN
In order to determine the status of heavy metal pollution in river sediments and wild fish in Xi'an, concentrations of heavy metals (Cr, Ni, Cu, Zn, As, and Pb) were collected and analyzed in sediments and wild fish during dry season (October-November 2020) and wet season (June-July 2021). This study aimed to investigate the spatial and temporal variations of heavy metals in urban rivers of Xi'an, China. Their distribution characteristics and sources as well their pollution levels and health risks were assessed. The findings revealed that influenced by human activities, the heavy metal content in sediments (mg·kg-1 dry weight) in wet season was ranked as follows: Cr (73.09) > Zn (63.73) > Pb (40.31) > Ni (31.52) > Cu (24.86) > As (6.83); in the dry season: Zn (94.07) > Cr (69.59) > Cu (34.24) > Ni (33.60) > Pb (32.87) > As (7.60). Moreover, 32 fish samples from six species indicated an average metal content trend (mg·kg-1 wet weight) of Zn (8.70) > Cr (0.57) > Pb (0.28) > Ni (0.27) > Cu (0.24) > As (0.05). The potential ecological risk indices for sediment heavy metal concentrations in both seasons were well below the thresholds, which indicates that the aquatic environment is in safe level. The analysis of the potential ecological risk of sediment heavy metal concentrations indicates that the aquatic environment is safe for the time being. Based on the estimated daily intake (EDI), target risk quotient (THQ), total target risk quotient (TTHQ), cancer risk (CR), total cancer risk (TCR), and the permissible safety limits set by the agencies, the consumption of the fish examined is safe for human health. However, the presence of Cr and As in wild fish should still be a concern for human health, especially for children. The cumulative effect of heavy metals and the bioconcentration factor (BCF) suggest that sediment and heavy metals in fish are closely related, with higher concentrations in fish living in the bottom layer of the water column than in other water layers, and increasing with increasing predator levels. Correlation analysis and PMF modeling identified and determined four comparable categories of potential sources, namely, (1) atmospheric deposition and traffic sources, (2) agricultural sources, (3) industrial sources, and (4) natural sources.
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Metales Pesados , Neoplasias , Contaminantes Químicos del Agua , Animales , Niño , Humanos , Estaciones del Año , Monitoreo del Ambiente , Ríos , Plomo/análisis , Sedimentos Geológicos/análisis , Metales Pesados/análisis , Medición de Riesgo , China , Peces , Agua/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
INTRODUCTION: The main aim of this study was to investigate the impact of isolated coronary microvascular disease (CMD) as diagnosed via various modalities on prognosis. METHODS: A systematic literature review of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to March 2023. Included studies were required to measure coronary microvascular function and report outcomes in patients without obstructive coronary artery disease (CAD) or any other cardiac pathological characteristics. The primary endpoint was all-cause mortality, and the secondary endpoint was a major adverse cardiac event (MACE). Pooled effects were calculated using random effects models. RESULTS: A total of 27 studies comprising 18,204 subjects were included in the meta-analysis. Indices of coronary microvascular function measurement included coronary angiography-derived index of microcirculatory resistance (caIMR), hyperemic microcirculatory resistance (HMR), coronary flow reserve (CFR), and so on. Patients with isolated CMD exhibited a significantly higher risk of mortality (OR: 2.97, 95% CI, 1.91-4.60, p < 0.0001; HR: 3.38, 95% CI, 1.77-6.47, p = 0.0002) and MACE (OR: 5.82, 95% CI, 3.65-9.29, p < 0.00001; HR: 4.01, 95% CI, 2.59-6.20, p < 0.00001) compared to those without CMD. Subgroup analysis by measurement modality demonstrated consistent and robust pooled effect estimates in various subgroups. CONCLUSION: CMD is significantly associated with an elevated risk of mortality and MACE in patients without obstructive CAD or any other identifiable cardiac pathologies. The utilization of various measurement techniques may have potential advantages in the management of isolated CMD.
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Enfermedad de la Arteria Coronaria , Humanos , Angiografía Coronaria/métodos , Microcirculación , Enfermedad de la Arteria Coronaria/complicaciones , PronósticoRESUMEN
Organic amine and nanosilica were combined to create a nano-demulsifier, which was employed in the oil-water separation process of a condensate emulsion. The nano-demulsifier has the structure of hyperbranched polymers and the skeleton structure of hyperbranched nanomaterials, and displays the demulsification impact of organic amine polymers as well as the synergistic effect of nanomaterials. This nano-demulsifier has the potential to drastically reduce the quantity of condensate demulsifiers utilized in the gathering station. The dehydration rate of the condensate lotion in the gas gathering station can reach more than 95% only at a concentration of 1.0 wt.%. Its application can significantly increase the separation efficiency of the condensate emulsion as well as the quality of condensate oil. It has a positive impact on cost reduction and efficiency in gas well production. The mechanism of action of the demulsifier was also studied, and the results show that the demulsifier is a phase reverse demulsifier.
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Tumor extracellular acidity and chemoresistance are regarded as the main obstacles to achieving optimal chemotherapeutic efficacy in tumor therapy. Herein, a new kind of acid-cascade P-S-Z nanoparticles (NPs) is developed to relieve extracellular acidosis and enhance chemotherapy without causing drug resistance. The P-S-Z NPs selectively accumulate in tumors and then regulate the release of S-Z NPs containing syrosingopine (Syr) and acid-activated prodrug ZMC1-Pt depending on the extracellular acidity. Benefiting from their small size and positive surface charge, S-Z NPs are easily internalized by tumor cells in deep tumor tissue, facilitating the release of Syr to inhibit lactic acid excretion and ultimately enhance cell acidosis. The prolonged intracellular acidosis not only inhibits tumor cell proliferation, but also continuously triggers the activation of ZMC1-Pt prodrug, a platinum-based chemotherapeutic drug that effectively eliminates cancer cells and restores wild-type p53 function to prevent tumor chemoresistance. As a proof of concept, this is a promising strategy to transfer the adverse effect of intracellular acidosis to facilitate chemotherapy. This well-designed delivery system effectively kills tumor cells without causing significant tumor drug resistance, thus opening a new window to treat cancer.
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Acidosis , Antineoplásicos , Nanopartículas , Profármacos , Humanos , Línea Celular Tumoral , Resistencia a Antineoplásicos , Acidosis/tratamiento farmacológicoRESUMEN
Introduction: This review aimed to elucidate the significance of information collaboration in the prevention and control of public health emergencies, and its evolutionary pathway guided by the theory of complex adaptive systems. Methods: The study employed time-slicing techniques and social network analysis to translate the dynamic evolution of information collaboration into a stage-based static representation. Data were collected from January to April 2020, focusing on the COVID-19 pandemic. Python was used to amass data from diverse sources including government portals, public commentary, social organizations, market updates, and healthcare institutions. Post data collection, the structures, collaboration objectives, and participating entities within each time slice were explored using social network analysis. Results: The findings suggest that the law of evolution for information collaboration in public health emergencies primarily starts with small-scale collaboration, grows to full-scale in the middle phase, and then reverts to small-scale in the final phase. The network's complexity increases initially and then gradually decreases, mirroring changes in collaboration tasks, objectives, and strategies. Discussion: The dynamic pattern of information collaboration highlighted in this study offers valuable insights for enhancing emergency management capabilities. Recognizing the evolving nature of information collaboration can significantly improve information processing efficiency during public health crises.
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COVID-19 , Humanos , COVID-19/epidemiología , Salud Pública , Urgencias Médicas , Pandemias , Red SocialRESUMEN
IMPORTANCE: Black solider fly larvae and the gut microbiota can recycle nutrients from various organic wastes into valuable insect biomass. We found that Citrobacter amalonaticus, a gut commensal bacterium of the insect, exerts beneficial effects on larval growth and development and that the expression of many metabolic larval genes was significantly impacted by the symbiont. To identify the larval genes involved in the host-symbiont interaction, we engineered the symbiont to produce double-strand RNA and enabled the strain to silence host genes in the larval gut environment where the interaction takes place. With this approach, we confirmed that two intestinal protease families are involved in the interaction and provided further evidence that intestinal protein metabolism plays a role in the interaction. This work expands the genetic toolkits available to study the insect functional genomics and host-symbiont interaction and provide the prospective for the future application of gut microbiota on the large-scale bioconversion.
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Dípteros , Humanos , Animales , Larva/microbiología , Estudios Prospectivos , Bacterias , SimbiosisRESUMEN
The endometrial lining of the uterus is essential for women's reproductive health and consists of several different types of epithelial and stromal cells. Although models such as gland-like structures (GLSs) and endometrial assembloids (EnAos) are successfully established, they lack an intact luminal epithelium, which makes it difficult to recapitulate endometrial receptivity. Here, a novel EnAo model (ALI-EnAo) is developed by combining endometrial epithelial cells (EnECs) and stromal cells (EnSCs) and using an improved matrix and air-liquid interface (ALI) culture method. ALI-EnAos exhibit intact EnSCs and glandular and luminal epithelia, which recapitulates human endometrium anatomy, cell composition, hormone-induced menstrual cycle changes, gene expression profiles, and dynamic ciliogenesis. The model suggests that EnSCs, together with the extracellular matrix and ALI culture conditions, contribute to EnAo phenotypes and characteristics reflective of the endometrial menstrual cycle. This enables to transcriptionally define endometrial cell subpopulations. It anticipates that ALI-EnAos will facilitate studies on embryo implantation, and endometrial growth, differentiation, and disease.
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Implantación del Embrión , Endometrio , Humanos , Femenino , Endometrio/metabolismo , Ciclo Menstrual , Epitelio , Células Epiteliales/metabolismoRESUMEN
Free energy perturbation coupled with replica exchange with solute tempering (FEP/REST) offers a rigorous approach to compute relative free energy changes for ligands. To determine the applicability of FEP/REST for the ligands with distributed binding poses, we considered two alchemical transformations involving three putative inhibitors I0, I1, and I2 of the Venezuelan equine encephalitis virus nuclear localization signal sequence binding to the importin-α (impα) transporter protein. I0 â I1 and I0 â I2 transformations, respectively, increase or decrease the polarity of the parent molecule. Our objective was three-foldâ(i) to verify FEP/REST technical performance and convergence, (ii) to estimate changes in binding free energy ΔΔG, and (iii) to determine the utility of FEP/REST simulations for conformational binding analysis. Our results are as follows. First, our FEP/REST implementation properly follows FEP/REST formalism and produces converged ΔΔG estimates. Due to ligand inherent unbinding, the better FEP/REST strategy lies in performing multiple independent trajectories rather than extending their length. Second, I0 â I1 and I0 â I2 transformations result in overall minor changes in inhibitor binding free energy, slightly strengthening the affinity of I1 and weakening that of I2. Electrostatic interactions dominate binding interactions, determining the enthalpic changes. The two transformations cause opposite entropic changes, which ultimately govern binding affinities. Importantly, we confirm the validity of FEP/REST free energy estimates by comparing them with our previous REST simulations, directly probing binding of three ligands to impα. Third, we established that FEP/REST simulations can sample binding ensembles of ligands. Thus, FEP/REST can be applied (i) to study the energetics of the ligand binding without defined poses and showing minor differences in affinities |ΔΔG| â² 0.5 kcal/mol and (ii) to collect ligand binding conformational ensembles.
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Simulación de Dinámica Molecular , Ligandos , Unión Proteica , Sitios de Unión , Entropía , TermodinámicaRESUMEN
Heavy metal pollution poses a great threat to the ecological environment and human health. In particular, copper ions (Cu2+) play a vital role in regulating fundamental life behavior, and the homeostasis of Cu2+ is closely related to many physiological processes. The excessive accumulation of Cu2+ in the human body through food and drinking water will cause severe diseases. However, current conventional Cu2+ detection methods for evaluating the content of Cu2+ are unable to meet the complete requirements of practical Cu2+ analysis in the practical aquatic environment. In this work, we successfully constructed a novel fluorescent DNA aptasensor, which originated from the binding reaction between the improved DNA fluorescent light-up aptamer termed S2T3AT-GC and a small fluorescent molecule termed DFHBI-1T (S2T3AT-GC/DFHBI-1T) to realize fast and anti-interference response for Cu2+via the competitive interaction between Cu2+ and S2T3AT-GC (Cu2+/S2T3AT-GC) destroying the contained G-quadruplex structure of S2T3AT-GC. Moreover, it enables the sensitive detection of Cu2+ with a detection limit of 0.3 µM and a wide detection linear range from 0.3 to 300 µM. Moreover, with the verification of high stability in real industrial sewage samples, this aptasensor exhibits excellent detection performance for Cu2+ analysis in real water samples. Therefore, the proposed aptasensor exhibits great potential in exploring Cu2+-related environmental and ecological research.
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Cobre , Aguas del Alcantarillado , Humanos , Cobre/análisis , Cobre/química , ADN , Iones , Colorantes Fluorescentes/químicaRESUMEN
Synthetic red fluorescent protein (RFP) chromophores have emerged as valuable tools for biological imaging and therapeutic applications, but their application in the visualization of endogenous RNA G-quadruplexes (G4s) in living cells has been rarely reported so far. Here, by integrating the group of the excellent G4 dye ThT, we modulate RFP chromophores to create a novel fluorescent probe DEBIT with red emission. DEBIT selectively recognizes the G4 structure with the advantage of strong binding affinity, high selectivity, and excellent photostability. Using DEBIT as a fluorescent indicator, the real-time monitoring of RNA G4 in biological systems can be achieved. In summary, our work expands the application of synthetic RFP chromophores and provides an essential dye category to the classical G4 probes.
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G-Cuádruplex , Colorantes Fluorescentes/química , Proteínas Luminiscentes/genética , ARN/química , Proteína Fluorescente RojaRESUMEN
This study examines the determinants that drive the behavior of sharing health information within online health communities. Leveraging the Theory of Planned Behavior, the Technology Acceptance Model, and the "Knowledge-Attitude-Practice" theory, a comprehensive model elucidating the key elements that sway the health information-sharing behavior among users of online health communities is designed. This model is validated through Structural Equation Modeling (SEM) and Fuzzy Set Qualitative Comparative Analysis (fsQCA). Findings derived from the SEM suggest that perceived ease of use, perceived usefulness, perceived trust, and perceived behavioral control exert a significant positive impact on attitudes towards health information sharing, the intention to share health information, and the actual health information-sharing behavior. The fsQCA unfolds two unique configuration path models that lead to the emergence of health information-sharing behavior: one predicated on perceived trust and sharing intention, and the other on perceived usefulness, behavioral control, and sharing attitude. This research provides invaluable insights, fostering a deeper comprehension of the dynamics involved in health information sharing within online communities, thereby directing the design of more effective health platforms to augment user engagement and enable informed health decisions.