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Impairments in working memory (WM) are evident in both clinically diagnosed patients with mild cognitive decline and older adults at risk, as indicated by lower scores on neuropsychological tests. Examining the WM-related neural signatures in at-risk older adults becomes essential for timely intervention. WM functioning relies on dynamic brain activities, particularly within the frontoparietal system. However, it remains unclear whether the cognitive decline would be reflected in the decreased dynamic reconfiguration of brain coactivation states during WM tasks. We enrolled 47 older adults and assessed their cognitive function using the Montreal Cognitive Assessment. The temporal dynamics of brain coactivations during a WM task were investigated through graph-based time-frame modularity analysis. Four primary recurring states emerged: two task-positive states with positive activity in the frontoparietal system (dorsal attention and central executive); two task-negative states with positive activity in the default mode network accompanied by negative activity in the frontoparietal networks. Heightened WM load was associated with increased flexibility of the frontoparietal networks, but the cognitive decline was correlated with reduced capacity for neuroplastic changes in response to increased task demands. These findings advance our understanding of aberrant brain reconfiguration linked to cognitive decline, potentially aiding early identification of at-risk individuals.
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Disfunción Cognitiva , Memoria a Corto Plazo , Humanos , Anciano , Memoria a Corto Plazo/fisiología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Cognición/fisiología , Disfunción Cognitiva/diagnóstico por imagen , Mapeo Encefálico , Pruebas Neuropsicológicas , Imagen por Resonancia MagnéticaRESUMEN
Nanozymes with multiple functionalities endow biochemical sensing with more sensitive and efficient analytical performance by widening the sensing modes. Meanwhile, the target-oriented design of multifunctional nanozymes for certain biosensing remains challenging. Herein, a constructive strategy of doping iron into polymer dots (PDs) to achieve nanozymes with excellent oxidase-mimicking and peroxidase-mimicking activity is proposed. Compared with the Fe-free PDs prepared under the same mild condition, the Fe-doped PDs (Fe-PDs) exhibit greatly boosted fluorescence at 500 nm. While applying 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate, the fluorescence of the Fe-PDs can be further quenched by oxTMB due to the inner filter effect (IFE). Inspired by this, a simple but efficient colorimetric and fluorometric dual-mode sensing platform is developed for monitoring the reducing substances ascorbic acid (AA), α-glucosidase (α-Glu), and its inhibitors (AGIs). We believe that such multifunctional enzyme-mimic materials will provoke the exploration of multimode sensing strategy with strong practicality to serve as a versatile tool in biochemical sensing.
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The advancement of acetylcholinesterase (AChE) activity and its inhibitor assays is crucial for clinical diagnosis, drug screening, and environmental monitoring. A nanozyme-mediated cascade reaction system could offer promising prospects for a wide range of applications in such biosensing; however, the creation of nanozyme catalysts with diverse functionalities remains a significant challenge. Herein, we have proposed a multifunctional iron-doped polymer dots (Fe-PDs) nanozyme possessing excellent fluorescence and peroxidase (POD)-mimicking activity. Notably, the Fe-PDs nanozyme is capable of catalyzing H2O2 to produce a series of reactive oxygen species, which can simultaneously quench the fluorescence of Fe-PDs and induce a chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB), enabling the dual-mode detection of H2O2 through both fluorescence turn-off and absorbance turn-on signals. Furthermore, by integrating acetylcholine (ACh) and choline oxidase (ChOx), we have developed a three-enzyme (AChE-ChOx-POD) cascade-based fluorometric and colorimetric dual-mode sensing platform for monitoring AChE activity and its inhibitors. The sensitive and convenient dual-mode sensor has achieved low limits of detection with 0.5 mU/mL (fluorometry) and 0.014 mU/mL (colorimetry) for AChE, respectively, which are superior to the traditional Ellman's assay. More significantly, this sensor can also be extended to detect the reversible and irreversible inhibitors of AChE, such as tacrine (IC50 = 23.3 nM) and carbaryl (LOD = 0.8 nM). We firmly believe that this innovative dual-mode nanozyme-involved multienzyme cascade system-based sensing strategy will stimulate further exploration and serve as a versatile and practical tool for biochemical sensing applications.
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Acetilcolinesterasa , Inhibidores de la Colinesterasa , Hierro , Polímeros , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/química , Inhibidores de la Colinesterasa/análisis , Inhibidores de la Colinesterasa/farmacología , Hierro/química , Polímeros/química , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/química , Puntos Cuánticos/química , Colorimetría/métodos , Colorantes Fluorescentes/química , Técnicas Biosensibles/métodos , Oxidorreductasas de Alcohol/metabolismo , Oxidorreductasas de Alcohol/antagonistas & inhibidores , Oxidorreductasas de Alcohol/química , Humanos , Bencidinas/química , Límite de DetecciónRESUMEN
Multiple enzyme-triggered cascade biocatalytic reactions are vital in vivo or vitro, considering the basic biofunction preservation in living organisms and signals transduction for biosensing platforms. Encapsulation of such enzymes into carrier endows a sheltering effect and can boost catalytic performance, although the selection and preparation of an appropriate carrier is still a concern. Herein, focusing on MAF-7, a category of metal azolate framework (MAF) with superiority against the topologically identical ZIF-8, this enzyme@MAF system can ameliorate the sustainability of encapsulating natural enzymes into carriers. The proposed biocatalyst composite AChE@ChOx@MAF-7/hemin is constructed via one-pot in situ coprecipitation method. Subsequently, MAF-7 is demonstrated to exhibit an excellent capacity of the carrier and protection against external factors in the counterpart of ZIF-8 through encapsulated and free enzymes. In addition, detections for specific substrates or inhibitors with favorable sensitivity are accomplished, indicating that the properties above expectation of different aspects of the established platform are successfully realized. This biofunctional composite based on MAF-7 can definitely provide a potential approach for optimization of cascade reaction and enzyme encapsulation.
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Biocatálisis , Técnicas Biosensibles , Interacciones Hidrofóbicas e Hidrofílicas , Técnicas Biosensibles/métodos , Materiales Biocompatibles/química , Estructuras Metalorgánicas/química , Enzimas/metabolismo , Enzimas/químicaRESUMEN
Climate change will likely increase habitat loss of endemic tree species and drives forest conversion in mountainous forests. Elevation gradients provide the opportunity to predict possible consequences of such changes. While species compositions of various taxa have been investigated along elevation gradients, data on trophic changes in soil-dwelling organisms are scarce. Here, we investigated trophic changes of the Collembola communities along the northern slope of Changbai Mountain, China. We sampled Collembola in primary forests at seven elevations (800-1700 m asl). We measured individual body lengths and bulk stable isotopes on species level. We further categorized Collembola species into life forms. The community-weighted means of Δ15N and Δ13C values as well as minimum Δ15N values and isotopic uniqueness of Collembola communities increased with increasing elevation, while the range of Δ15N values decreased. Maximum and minimum of Δ13C values differed between elevations but showed no linear trend. Further, Δ15N values of Collembola species occurring across all elevations increased with elevation. Changes in Δ15N values with elevation were most pronounced in hemiedaphic species, while Δ13C values increased strongest with elevation in euedaphic species. Δ15N values increased with decreasing body size in hemiedaphic and euedaphic species. Overall, the results suggest that Collembola species functioning as primary decomposers at lower elevations shift towards functioning as secondary decomposers or even predators or scavengers at higher elevation forests. The results further indicate that access to alternative food resources depends on Collembola life form as well as body size and varies between ecosystems.
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Ecosistema , Bosques , Árboles , Isótopos de Carbono/análisis , Tamaño CorporalRESUMEN
BACKGROUND: Stress urinary incontinence (SUI), the prevalent form of urinary incontinence, significantly impairs women's quality of life. This study aims to create a visual nomogram to estimate the risk of SUI within one year postpartum for early intervention in high-risk Chinese women. METHODS: We recruited 1,531 postpartum women who gave birth at two hospitals in Kunshan City from 2021 to 2022. Delivery details were meticulously extracted from the hospitals' medical records system, while one-year postpartum follow-ups were conducted via phone surveys specifically designed to ascertain SUI status. Utilizing data from one hospital as the training set, logistic regression analysis was performed to pinpoint significant factors and subsequently construct the nomogram. To ensure robustness, an independent dataset sourced from the second hospital served as the external validation cohort. The model's performance was rigorously evaluated using calibration plots, ROC curves, AUC values, and DCA curves. RESULTS: The study population was 1,125 women. The SUI incidence within one year postpartum was 26% (293/1125). According to the regression analysis, height, pre-pregnancy BMI, method of induction, mode of delivery, perineal condition, neonatal weight, SUI during pregnancy, and SUI during the first pregnancy were incorporated into the nomogram. The AUC of the nomogram was 0.829 (95% CI 0.790-0.867), and the external validation set was 0.746 (95% CI 0.689-0.804). Subgroup analysis based on parity showed good discrimination. The calibration curve indicated concordance. The DCA curve showed a significant net benefit. CONCLUSION: Drawing from real-world data, we have successfully developed an SUI predictive model tailored for postpartum Chinese women. Upon successful external validation, this model holds immense potential as an effective screening tool for SUI, enabling timely interventions and ultimately may improve women's quality of life.
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Nomogramas , Incontinencia Urinaria de Esfuerzo , Humanos , Femenino , Incontinencia Urinaria de Esfuerzo/epidemiología , Incontinencia Urinaria de Esfuerzo/diagnóstico , Adulto , Estudios Retrospectivos , China/epidemiología , Embarazo , Periodo Posparto , Factores de Riesgo , Incidencia , Medición de Riesgo/métodos , Calidad de Vida , Pueblos del Este de AsiaRESUMEN
Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique that can modulate cortical excitability and behavioral performance. However, its effects on spontaneous low-frequency fluctuations of brain activity are still poorly understood. Here, we systematically investigated the frontopolar tDCS effects on resting-state brain activity and connectivity. Twelve healthy participants were recruited and received anode, cathode, and sham stimulation in a randomized order. Resting-state functional magnetic resonance imaging was performed before and after stimulation. Functional connectivity was calculated to examine tDCS effects within and beyond the frontopolar network. To assess the frequency-dependent changes of brain activity, fractional amplitude of low-frequency fluctuations (fALFF) was computed in the slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands. The results showed anodal tDCS-induced widespread connectivity reduction within and beyond the frontopolar network. Regardless of tDCS polarity, stimulation effect on fALFF was significantly larger in slow-5 band compared with the slow-4. Notably, anodal tDCS-induced connectivity changes were associated with pre-tDCS fALFF in slow-4 band, showing positive correlations in the frontal regions and negative correlations in the temporal regions. Our findings imply that tDCS-induced brain alterations may be frequency-dependent, and pre-tDCS regional brain activity could be used to predict post-tDCS connectivity changes.
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Excitabilidad Cortical , Estimulación Transcraneal de Corriente Directa , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Mapeo Encefálico/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Estimulación Transcraneal de Corriente Directa/métodosRESUMEN
The absorption and accumulation of nanoplastics (NPs) by plants is currently attracting considerable attention. NPs also tend to adsorb surrounding organic pollutants, such as pesticides, which can damage plants. However, molecular mechanisms underlying the phytotoxicity of NPs are not sufficiently researched. Therefore, we analyzed the toxicological effects of 50 mg/L polystyrene NPs (PS 50 nm) and 5 mg/L the herbicide quinolinic (QNC) on rice (Oryza sativa L.) using 7-day hydroponic experiments, explaining the corresponding mechanisms by transcriptome analysis. The main conclusion is that all treatments inhibit rice growth and activate the antioxidant level. Compared with CK, the inhibition rates of PS, QNC, and PS+QNC on rice shoot length were 3.95%, 6.68%, and 11.43%, respectively. The gene ontology (GO) term photosynthesis was significantly enriched by QNC, and the combination PS+QNC significantly enriched the GO terms of amino sugar and nucleotide sugar metabolisms. The chemicals QNC and PS+QNC significantly affected the Kyoto Encyclopedia of Genes and Genomes (KEGG) of the MAPK signaling pathway, plant hormone signal transduction, and plant-pathogen interaction. Our findings provide a new understanding of the phytotoxic mechanisms and environmental impacts of the interactions between NPs and pesticides. It also provides insights into the impact of NPs and pesticides on plants in the agricultural system.
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Oryza , Plaguicidas , Transcriptoma , Oryza/metabolismo , Poliestirenos/metabolismo , Microplásticos/metabolismo , Plaguicidas/metabolismoRESUMEN
Soil quality and function in forest environments are influenced by the interaction of soil-forming parameters and silvicultural systems. Hyrcanian forests were recently accepted as a UNESCO World Heritage Site, which extends across an area of approximately 1.8 million hectares and ascend to an elevation of 2800 m above sea level (m.a.s.l). In these woodlands, Oriental Beech (Fagus orientalis Lipsky) is the predominant tree species and could be observed at 700-1500 m.a.s.l., and occur on different parent rocks. Shelterwood and single-tree selection techniques have been the primary management methods for beech forests for the past forty years. Studies investigating the impacts of silvicultural systems have not yet been done on soil and forest floor features on different bedrock geology and altitudes. Therefore, in this study, we examined the influence of single-tree selection and shelterwood methods, 25 years after employing those methods, on soil quality and function compared to control areas (intact forests) in Hyrcanian beech stands. For this purpose, 15 forest floor (30 × 30 cm) and topsoil (0-10 cm depth) samples in each silvicultural systems (i.e., single-tree selection and shelterwood methods and control zones) × 4 regions (including Rasht, Nowshahr, Sari and Gorgan) × 4 altitude levels (with averages of 800, 1000, 1200 and 1400 m.a.s.l.) were considered. According to our findings, the investigated forest regions, forest floor and soil characteristics across various locations spots could be separated by principal component analysis output, and more than 85% of the variance was explained by the first and second axes. The structural equation model showed that the region, altitude and silvicultural systems had an effective role in the changes in soil biological activities by influencing the forest floor, and the soil physicochemical features. Based upon the network model, the C/N ratio, the sand content, the soil aggregate stability, the available K, the fulvic acid, and the Acarina density were found to be prominent factors with regard to soil function. In the control sites, increased soil organic material fractions, microbial/enzyme and biota activities were detected, particularly at the lower altitudes of the Nowshahr site, which had geological formations of dolomite and calcic layers. Taken together, it seems that the single-tree method, commonly referred to as the close-to-nature technique produces more suitable conditions for soil functioning compared to the shelterwood management approach. Silvicultural systems, bedrock geology and altitude can have major detrimental effects on soil function and fertility, over the long-term, impacts may increase with harvest intensity.
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Fagus , Suelo , Suelo/química , Altitud , Geología , Bosques , BiotaRESUMEN
BACKGROUND: To investigate the structural and functional changes of the retina in patients with different degrees of internal carotid artery (ICA) stenosis. METHODS: This cross-sectional study included patients with varying degrees ICA stenosis. Clinical characteristics of 41 patients were collected after being divided into four groups according to the ICA stenosis indicated by computed tomographic angiography (Group 0: without ICA stenosis, Group 1: ipsilateral slight ICA stenosis, Group 2: ipsilateral moderate ICA stenosis, Group 3: ipsilateral severe ICA stenosis). Retinal vessel caliber (RVC) was measured quantitatively with the Integrative Vessel Analysis software. The retinal sensitivity was examined with the MP-3 microperimeter. The relationships among central retinal artery equivalent (CRAE), central retinal vein equivalent, arteriole to venule ratio (AVR), mean retinal sensitivity (MS) and ICA stenosis degree were analysed. RESULTS: The CRAE in Group 3 were significantly smaller compared with Group 0, Group 1 and Group 2 (P < 0.001, P < 0.001, P = 0.002). Significant decrease was found between Group 3 with other groups in MS at fovea (P < 0.001, P < 0.001, P = 0.002). Moreover, there was a positive correlation found between MS and CRAE (Beta = 0.60, P < 0.001 at fovea; Beta = 0.64, P < 0.001 at 2 degree; Beta = 0.60, P < 0.001 at 4 degree; Beta = 0.55, P < 0.001 at 8 degree; Beta = 0.53, P < 0.001 at 12 degree). CONCLUSIONS: The present study revealed smaller CRAE and AVR in ipsilateral severe ICA stenosis patients. And the MS decreased in patients with severe ICA stenosis. In addition, MS had a positive correlation with CRAE.
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Estenosis Carotídea , Arteria Retiniana , Arteria Carótida Interna , Estenosis Carotídea/diagnóstico por imagen , Estudios Transversales , Humanos , RetinaRESUMEN
Color-rendering manipulation of solar cells is drawing increasing interest, since the integration of color displaying can promote various advanced applications. However, the dual functionality of high-performance operation and easy processing remain a challenge. Here we propose a colorful perovskite solar cell (PSC) based on purely planar layers. The photonic crystal (PC), which does not interfere with the PSC processing, enables the display of high-purity colors and maintaining the number of PC layers at 4-6. The fabricated PSC with a four-layer PC successfully displays red-green-blue (RGB) colors, with the power-conversion efficiency of 10.94%, 11.01%, and 13.70%, respectively. Further study indicates that by employing a six-layer PC the PSC can obtain excellent color-displaying effect with the color gamut up to 81.8% of the standard RGB. It also shows that the design has a good tolerance to the deviation of layer thickness.
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During the summer of 2015, polycyclic aromatic hydrocarbons (PAHs) in the atmosphere were collected by passive air samplers in typical urban-rural fringe of Wuhan-Ezhou region, Central China. The results showed that 16 kinds of PAHs were ubiquitous with the concentrations of ∑16PAHs from 14.69 to 136.30 ng·m-3 and the mean concentration of 43.03 ng·m-3. Phenanthrene (Phe), fluoranthene (Fla) and pyrene (Pyr) were major components, which accounted for 81% of ∑16PAHs. PAHs atmospheric concentrations presented obvious spatial variation, being significantly related to geographical environment and influenced by anthropogenic activity. Air-soil exchange status of PAHs was discussed according to the fugacity fraction (ff). The results showed that HMW-PAHs behaved as net deposition, while LMW-PAHs were more likely to establish dynamic equilibrium between atmosphere and soil than MMW-PAHs and HMW-PAHs. For some PAHs, such as acenaphthylene (Acy) and anthracene (Ant), the soil acted as second sources of them.
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Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Hidrocarburos Policíclicos Aromáticos/análisis , Atmósfera , China , Fluorenos , Pirenos , Estaciones del Año , Suelo , Contaminantes del Suelo/análisisRESUMEN
IMM-H004 [7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin] is a novel derivative of coumarin, which played neuroprotective roles in brain ischemia in rats in previous studies. Although antiapoptosis and improving synapsis structure were proved, the effects and mechanisms of IMM-H004 in brain ischemia need further study. In this paper, the effect of IMM-H004 on H2O2-induced neurotoxicity in pheochromocytoma (PC12) cells was researched. Morphological observation, MTT method and PI/Hoechst staining were used to indicate cell viability and apoptosis. JC-1 and DCFH-DA were used to test mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), respectively. The antioxidative activity was detected by Glutathione (GSH) and Total Antioxidant Capacity (TAC) Assay kits. Western blot was used to test apoptosis related proteins. Our results showed that treatment with 1-10 µM IMM-H004 markedly increased cell viability and decreased cell apoptosis induced by H2O2. Moreover, 1-10 µM IMM-H004 could enhance MMP and protect mitochondrial function. 1-10 µM IMM-H004 also could lower the ROS and raise the GSH and TAC level. Furthermore, 1-10 µM IMM-H004 could decrease the ratio of Bax/Bcl-2 and increase the ratio of p-AKT/AKT, which were related to apoptosis and survival. All these indicated that IMM-H004 protects PC12 cells against H2O2-induced neurotoxicity. Antioxidative and antiapoptosis may be the mechanisms of IMM-H004 in brain ischemia. These studies indicate that IMM-H004 might be a potential drug for treatment brain ischemia.
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Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Cumarinas/farmacología , Peróxido de Hidrógeno/toxicidad , Fármacos Neuroprotectores/farmacología , Animales , Antioxidantes/química , Apoptosis/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Cumarinas/química , Relación Dosis-Respuesta a Droga , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Fármacos Neuroprotectores/química , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Células PC12 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVES: To investigate bioavailability enhancement of zinc on model oral surfaces and in oral biofilms in vitro through strategic formulation with two sources of zinc and L-arginine. METHODS: To modulate the bioavailability of active zinc ions in a zinc citrate dentifrice, an additive research strategy was pursued. A series of zinc citrate dentifrice formulations were prepared with increasing replacement of zinc citrate with zinc oxide (a water insoluble source of zinc ions) to generate a Dual Zinc active system. A screening of isolated zinc and amino acid effects in simple solutions using zeta potential and uptake to model oral surfaces was performed in an effort to determine the effect of particle charge on zinc bioavailability. Zinc delivery and antibacterial efficacy of the Dual Zinc plus Arginine dentifrice formula were tested using in vitro oral epithelial tissue and saliva-derived biofilm models. Furthermore, zinc penetration and retention were determined by subjecting in vitro biofilms to dynamic flow after treatment with the Dual Zinc plus Arginine dentifrice with treated biofilms evaluated for zinc using imaging mass spectrometry (I-MS). Bacterial adhesion to gingival epithelial cells treated with the Dual Zinc plus Arginine dentifrice was imaged upon challenging with Streptococcus gordonii. RESULTS: Addition of zinc oxide into a zinc citrate dentifrice formula enhanced the efficacy of the system against anaerobic biofilms in a concentration- dependent manner. L-arginine further provided a significant positive charge (+36 mV) to the zinc oxide suspension (+16 mV) as measured by zeta potential. Simple solutions of the Dual Zinc active showed increased zinc uptake on model oral surfaces as a direct function of L-arginine concentration. Antibacterial efficacy of a Dual Zinc plus Arginine dentifrice was evaluated through multiple mechanisms. Enhanced antibacterial performance was observed through significant reductions in metabolic activity as measured through bacterial glycolytic function (p = 0.0001) and total oxygen consumption (p = 0.0001). Greater penetration and retention of zinc was observed in bacterial biofilms treated with the Dual Zinc plus Arginine dentifrice in comparison to treatment with a Dual Zinc dentifrice after twelve hours of dynamic flow (10 mL/hour) in an in vitro drip flow biofilm culture. Confocal microscopy showed adherent bacteria on cheek cells treated with the Dual Zinc plus Arginine dentifrice formula. CONCLUSIONS: The combination of zinc citrate, zinc oxide, and the amino acid L-arginine in a dentifrice formula enhances the bioavailability of zinc to model oral tissue surfaces, resulting in unique physicochemical effects. The significant antimicrobial control associated with the Dual Zinc plus Arginine dentifrice provides a unique vehicle toward achieving whole mouth health.
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Placa Dental , Dentífricos , Zinc , Arginina , Disponibilidad Biológica , Placa Dental/prevención & control , Dentífricos/farmacocinética , Humanos , Zinc/farmacocinéticaRESUMEN
BACKGROUND: Clinical and social services both are important for dementia care. The International Dementia Alliance (IDEAL) Schedule for the Assessment and Staging of Care was developed to guide clinical and social care for dementia. Our study aimed to assess the validity and reliability of the IDEAL schedule in China. METHODS: Two hundred eighty-two dementia patients and their caregivers were recruited from 15 hospitals in China. Each patient-caregiver dyad was assessed with the IDEAL schedule by a rater and an observer simultaneously. The Clinical Dementia Rating (CDR), Mini-Mental Status Examination (MMSE), and Caregiver Burden Inventory (CBI) were assessed for criterion validity. IDEAL repeated assessment was conducted 7-10 days after the initial interview for 62 dyads. RESULTS: Two hundred seventy-seven patient-caregiver dyads completed the IDEAL assessment. Inter-rater reliability for the total score of the IDEAL schedule was 0.93 (95%CI = 0.92-0.95). The inter-class coefficient for the total score of IDEAL was 0.95 for the interviewers and 0.93 for the silent raters. The IDEAL total score correlated with the global CDR score (ρ = 0.72, p < 0.001), the CDR-sum of box (CDR-SOB, ρ = 0.74, p < 0.001), the total score of MMSE (ρ = -0.65, p < 0.001) and CBI (ρ = 0.70, p < 0.001). All item scores of the IDEAL schedule were associated with the CDR-SOB (ρ = 0.17 ~ 0.79, all p < 0.05). CONCLUSION: The IDEAL schedule is a valid and reliable tool for the staging of care for dementia in the Chinese population.
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Cuidadores/psicología , Demencia/diagnóstico , Demencia/enfermería , Encuestas y Cuestionarios/normas , Adaptación Psicológica , Anciano , Anciano de 80 o más Años , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Reproducibilidad de los ResultadosRESUMEN
We report a platform for the ratiometric fluorescent sensing of endogenously generated gaseous transmitter H2S in its aqueous form (bisulfide or hydrogen sulfide anion) based on the alteration of Förster resonance energy transfer from an emissive semiconductor quantum dot (QD) donor to a dithiol-linked organic dye acceptor. The disulfide bridge between the two chromophores is cleaved upon exposure to bisulfide, resulting in termination of FRET as the dye diffuses away from the QD. This results in enhanced QD emission and dye quenching. The resulting ratiometric response can be correlated quantitatively to the concentration of bisulfide and was found to have a detection limit as low as 1.36 ± 0.03 µM. The potential for use in biological applications was demonstrated by measuring the response of the QD-based FRET sensor microinjected into live HeLa cells upon extracellular exposure to bisulfide. The methodology used here is built upon a highly multifunctional platform that offers numerous advantages, such as low detection limit, enhanced photochemical stability, and sensing ability within a biological milieu.
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Transferencia Resonante de Energía de Fluorescencia , Colorantes Fluorescentes/química , Sulfuro de Hidrógeno/análisis , Colorantes Fluorescentes/síntesis química , Células HeLa , Humanos , Microscopía Fluorescente , Estructura Molecular , Puntos Cuánticos , Solubilidad , Células Tumorales Cultivadas , Agua/químicaRESUMEN
The human pathogen Pseudomonas aeruginosa coordinates the expression of virulence factors by using quorum sensing (QS), a signaling cascade triggered by the QS signal molecule and its receptor, a member of the LuxR family of QS transcriptional factors (LasR). The QS threshold and response in P. aeruginosa is defined by a QS LasR-specific antiactivator (QslA), which binds to LasR and prevents it from binding to its target promoter. However, how QslA binds to LasR and regulates its DNA binding activity in QS remains elusive. Here we report the crystal structure of QslA in complex with the N-terminal ligand binding domain of LasR. QsIA exists as a functional dimer to interact with the LasR ligand binding domain. Further analysis shows that QsIA binding occupies the LasR dimerization interface and consequently disrupts LasR dimerization, thereby preventing LasR from binding to its target DNA and disturbing normal QS. Our findings provide a structural model for understanding the QslA-mediated antiactivation mechanism in QS through protein-protein interaction.
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Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Modelos Moleculares , Multimerización de Proteína , Pseudomonas aeruginosa/química , Pseudomonas aeruginosa/metabolismo , Percepción de Quorum/fisiología , Transactivadores/química , Transactivadores/metabolismo , Proteínas Bacterianas/genética , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Humanos , Unión Proteica , Estructura Terciaria de Proteína , Pseudomonas aeruginosa/genética , Transactivadores/genéticaRESUMEN
Many bacterial pathogens produce diffusible signal factor (DSF)-type quorum sensing (QS) signals in modulation of virulence and biofilm formation. Previous work on Xanthomonas campestris showed that the RpfC/RpfG two-component system is involved in sensing and responding to DSF signals, but little is known in other microorganisms. Here we show that in Burkholderia cenocepacia the DSF-family signal cis-2-dodecenoic acid (BDSF) negatively controls the intracellular cyclic dimeric guanosine monophosphate (c-di-GMP) level through a receptor protein RpfR, which contains Per/Arnt/Sim (PAS)-GGDEF-EAL domains. RpfR regulates the same phenotypes as BDSF including swarming motility, biofilm formation, and virulence. In addition, the BDSF(-) mutant phenotypes could be rescued by in trans expression of RpfR, or its EAL domain that functions as a c-di-GMP phosphodiesterase. BDSF is shown to bind to the PAS domain of RpfR with high affinity and stimulates its phosphodiesterase activity through induction of allosteric conformational changes. Our work presents a unique and widely conserved DSF-family signal receptor that directly links the signal perception to c-di-GMP turnover in regulation of bacterial physiology.
Asunto(s)
Burkholderia cenocepacia/genética , Ácidos Grasos Monoinsaturados/química , Guanosina Monofosfato/química , Percepción de Quorum/genética , Receptores de Superficie Celular/química , Proteínas Bacterianas/metabolismo , Burkholderia cenocepacia/metabolismo , Comunicación Celular , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Dimerización , Modelos Genéticos , Mutagénesis , Mutación , Fenotipo , Unión Proteica , Receptores de Superficie Celular/metabolismo , Transducción de Señal , VirulenciaRESUMEN
The regulation of mRNA degradation is critical for proper gene expression. Many major pathways for mRNA decay involve the removal of the 5' 7-methyl guanosine (m(7)G) cap in the cytoplasm to allow for 5'-to-3' exonucleolytic decay. The most well studied and conserved eukaryotic decapping enzyme is Dcp2, and its function is aided by co-factors and decapping enhancers. A subset of these factors can act to enhance the catalytic activity of Dcp2, while others might stimulate the remodeling of proteins bound to the mRNA substrate that may otherwise inhibit decapping. Structural studies have provided major insights into the mechanisms by which Dcp2 and decapping co-factors activate decapping. Additional mRNA decay factors can function by recruiting components of the decapping machinery to target mRNAs. mRNA decay factors, decapping factors, and mRNA substrates can be found in cytoplasmic foci named P bodies that are conserved in eukaryotes, though their function remains unknown. In addition to Dcp2, other decapping enzymes have been identified, which may serve to supplement the function of Dcp2 or act in independent decay or quality control pathways. This article is part of a Special Issue entitled: RNA Decay mechanisms.
Asunto(s)
Endorribonucleasas/genética , Caperuzas de ARN/genética , Estabilidad del ARN/genética , Catálisis , Citoplasma , Endorribonucleasas/química , Eucariontes/enzimología , Eucariontes/genética , Humanos , Conformación Proteica , Estructura Terciaria de Proteína , Análogos de Caperuza de ARN/química , Análogos de Caperuza de ARN/genética , Caperuzas de ARN/químicaRESUMEN
Older adults often have difficulty in making decisions under uncertainty, increasing the risk of financial exploitation. However, it is still under investigation about the extent to which cognitive decline influences risky decision-making and the underlying neural correlates. We hypothesized that the individual differences of risk-taking behavior depend on cognitive integrity, in which the dorsal and ventral fronto-amygdala connectivity would play dissociable roles. In the current study, thirty-six young and 51 older adults were tested with the Iowa gambling task combing resting-state and task-related functional magnetic resonance imaging. The results showed significant changes in behaviors and the fronto-amygdala network in older adults relative to young adults. More importantly, age-effect on risk-taking behaviors was remarkably different in cognitively normal and impaired older adults. In resting-state analysis, task performance was positively correlated with the ventral fronto-amygdala connectivity and negatively correlated with the dorsal fronto-amygdala connectivity in cognitively impaired older adults, compared with cognitively normal individuals. Furthermore, task-related analysis confirmed the relationships between dorsal/ventral fronto-amygdala network and risk-taking behaviors depending on cognitive integrity. These findings indicate that the fronto-amygdala network is crucial for understanding altered risky decision-making in aging, suggesting dissociable contributions of the dorsal and ventral pathways in the context of cognitive decline.