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Persistent neuroinflammation and progressive neuronal loss are defining features of acute brain injury including traumatic brain injury (TBI) and cerebral stroke. Microglia, the most abundant type of brain-resident immune cells, continuously surveil the environment and play a central role in shaping the inflammatory state of the central nervous system (CNS). In the study, we discovered that the protein expression of METTL3 (a m6A methyltransferase) was upregulated in inflammatory microglia independent of increased Mettl3 gene transcription following TBI in both human and mouse subjects. Subsequently, we identified TRIP12, a HECT-domain E3 ubiquitin ligase, as a negative regulator of METTL3 protein expression by facilitating METTL3 K48-linked polyubiquitination. Importantly, selective ablation of Mettl3 inhibited microglial pathogenic activities, diminished neutrophil infiltration, rescued neuronal loss and facilitated functional recovery post-TBI. Using MeRIP-seq and CUT&Tag sequencing, we identified that METTL3 promoted the expression of Basic Leucine Zipper Transcriptional Factor ATF-Like (BATF), which in turn directly bound to a cohort of characteristic inflammatory cytokines and chemokine genes. Enhanced activities of BATF in microglia elicited TNF-dependent neurotoxicity and can also promote neutrophil recruitment through releasing CXCL2. Pharmacological inhibition of METTL3 using a BBB-penetrating drug-loaded nano-system showed satisfactory therapeutic effects in both TBI and stroke mouse models. Collectively, our findings identified METTL3-m6A-BATF axis as a potential therapeutic target for terminating detrimental neuroinflammation and progressive neuronal loss following acute brain injury. METTL3 protein is significantly up-regulated in inflammatory microglia due to the decreased proteasomal degradation mediated by TRIP12 and ERK-USP5 pathways. METTL3 stabilized BATF mRNA stability and promoted BATF expression through the m6A-IGF2BP2-dependent mechanism. Elevated expression of BATF elicits a pro-inflammatory gene program in microglia, and aggravates neuroinflammatory response including local immune responses and peripheral immune cell infiltration. Genetic deletion or pharmaceutically targeting METTL3-BATF axis suppressed microglial pro-inflammatory activities and promoted neurological recovery following TBI and stroke.
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Flame retardants could improve the safety properties of lithium batteries (LBs) with the sacrifice of electrochemical performance due to parasitic reactions. To concur with this, we designed thermal-response clothes for hexachlorophosphazene (HCP) additives by the microcapsule technique with urea-formaldehyde (UF) resin as the shell. HCP@UF combines with polyacrylonitrile (PAN) by hydrogen bonds successfully to form PAN-HCP@UF as the flame-retardant solid polymer electrolyte. The hydrogen bonds ensure excellent mechanical properties of the polymer electrolyte. The multiscale free radical-annihilating agent HCP effectively eliminates hydrogen free radicals of electrolytes under high temperature, showing excellent flame retardation. During the operation of the battery, functional groups on the UF resin act as active sites to promote the migration of lithium ions, while the internal HCP is protected from electrochemical reaction. With 25% HCP@UF addition, the limiting oxygen index of the PAN-HCP@UF increases to 28% and the Li+ transfer number up to 0.80. By UF protection, the initial capacity retention rate of the Li||LFP battery that assembles with PAN-HCP@UF is 88.8% after 500 cycles at 0.5 C. Thus, the microcapsule-encapsulated approach is deemed to provide an innovative strategy to prepare high-safety solid-state LB with a stable long cycle life.
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BACKGROUND: While many studies have established a positive correlation between adolescents' internet addiction and mental health problems, most of these studies have overlooked the internal heterogeneity of Internet addiction. This study aims to identify latent profiles among adolescents based on their Internet addiction and to examine the differences in aggression, depression, and anxiety across these profiles. METHODS: We conducted a survey involving 7422 adolescents and administered the Young's Internet Addiction Test, Aggression Behavior Questionnaire, Patient Health Questionnaire-9, and Generalized Anxiety Disorder Scale. Latent profile analysis was utilized to categorize Internet addiction profiles among adolescents. Associations between Internet addiction profiles and related factors were examined using the Bolck-Croon-Hagenaars method. RESULTS: Latent profile analysis suggested four profiles of Internet addiction, which were labeled: Regular, Risk, Low Internet addiction, and Internet addiction. The Internet addiction profile showed higher levels of aggression, depression, and anxiety than the Low Internet addiction profile. The Low Internet addiction profile had higher levels of aggression, depression, and anxiety than the Risk profile. The Risk profile demonstrated higher levels of aggression, depression, and anxiety when compared to the Regular profile. LIMITATIONS: Limitations include the cross-sectional design and the self-report measures. CONCLUSIONS: The identified Internet addiction profiles offer differential predictions for aggression, depression, and anxiety. These results underscore the significance of employing latent profile analysis when exploring the associations between Internet addiction and mental health issues.
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Agressão , Ansiedade , Depressão , Transtorno de Adição à Internet , Humanos , Adolescente , Agressão/psicologia , Masculino , Transtorno de Adição à Internet/epidemiologia , Transtorno de Adição à Internet/psicologia , Feminino , Depressão/epidemiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudos Transversais , Inquéritos e Questionários , Comportamento Aditivo/psicologia , Comportamento Aditivo/epidemiologia , Comportamento do Adolescente/psicologia , Internet , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Análise de Classes LatentesRESUMO
Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.
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Apoptose , Lesões Encefálicas Traumáticas , Fibronectinas , Camundongos Knockout , Mitocôndrias , Neurônios , Estresse Oxidativo , Sirtuína 3 , Animais , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/genética , Sirtuína 3/metabolismo , Sirtuína 3/genética , Fibronectinas/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Camundongos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Dinâmica MitocondrialRESUMO
Diabetes is a common chronic metabolic disease. The frequent fluctuation of glucose is the main cause of most diabetes complications, which in turn causes harm to the health of patients. Surface-enhanced Raman scattering (SERS) spectroscopy has attracted much attention in the rapid detection of glucose due to its unique molecular fingerprinting ability, ultra-high sensitivity and fast response. However, due to the low affinity between glucose and SERS substrate, poor signal, susceptibility to complex environmental interference, and poor stability of SERS detection, it is still a challenge for SERS to accurately and sensitively determine glucose in complex environments. In this work, we encapsulated 4-mercaptobutyronitrile (4-MBN) as an internal standard (IS) in Au@Ag NRs inside and then Au@4-MBN@Ag NRs, Leucomalachite Green (LMG), glucose oxidase (GOx) and horseradish peroxidase (HPR) were encapsulated in ZIF-8 to prepare a tandem enzyme catalytic ratiometric SERS sensor Au@4-MBN@Ag@LMG@ZIF-8(GOx, HPR) for the detection of glucose in saliva. Because ZIF-8 enhanced the catalytic activity of the enzyme, the ability of glucose enrichment, and weakens the aggregation of Ag NRs. The internal standard signal molecule improves the accuracy and sensitivity of detection. The ratiometric Raman signal I412/I2233 of glucose has a good linear relationship with the concentration in the range of 0.1-100 µM, and the limit of detection (LOD) could be down to 0.03 µM. At the same time, it has excellent selectivity, repeatability and accuracy. The recovery rate of glucose in saliva is 96.50%-105.56 %, which proves the feasibility of the method. The Au@4-MBN@Ag@LMG@ZIF-8(GOx, HPR) sensor prepared in this study showed excellent SERS performance, which was able to detect glucose quickly, sensitively and accurately. This work provides a new strategy for the design of enzyme-catalyzed SERS sensors.
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Glucose , Análise Espectral Raman , Humanos , Análise Espectral Raman/métodos , Glucose Oxidase/químicaRESUMO
BACKGROUND: Low-frequency noise may cause changes in cognitive function. However, there is no established consensus on the effect of low-frequency noise on cognitive function. Therefore, this systematic review and meta-analysis aimed to explore the relationship between low-frequency noise exposure and cognitive function. METHODS: We conducted a systematic review and identified original studies written in English on low-frequency noise and cognition published before December 2022 using the PsycINFO, PubMed, Medline, and Web of Science databases. The risk of bias was evaluated according to established guidelines. A random-effects meta-analysis was performed where appropriate. To explore the association between low-frequency noise exposure and cognitive function, we reviewed eight relevant studies. These studies covered cognitive functions grouped into four domains: attention, executive function, memory, and higher-order cognitive functions. The data extraction process was followed by a random-effects meta-analysis for each domain, which allowed us to quantify the overall effect. RESULTS: Our analysis of the selected studies suggested that interventions involving low-frequency noise only had a negative impact on higher-order cognitive functions (Z = 2.42, p = 0.02), with a standardized mean difference of -0.37 (95% confidence interval: -0.67, -0.07). A moderate level of heterogeneity was observed among studies (p = 0.24, I2 = 29%, Tau2 = 0.03). CONCLUSIONS: Our study findings suggest that low-frequency noise can negatively impact higher-order cognitive functions, such as logical reasoning, mathematical calculation, and data processing. Therefore, it becomes important to consider the potential negative consequences of low-frequency noise in everyday situations, and proactive measures should be taken to address this issue and mitigate the associated potential adverse outcomes.
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Cognição , Função Executiva , Humanos , Resolução de Problemas , Consenso , Bases de Dados FactuaisRESUMO
This study examined the feasibility of using tailored text messages to promote adherence to longitudinal protocols and determined what facets of text message tone influence motivation. Forty-three older adults (Mage = 73.21, SD = 5.37) were recruited to engage in video-game-based cognitive training for 10 consecutive days. Participants received encouraging text messages each morning that matched their highest or lowest ranking reasons for participating in the study, after which they rated how effective each message was in motivating them to play the games that day. After 10 days, participants rated all possible messages and participated in semi-structured interviews to elicit their preferences for these messages. Results showed that messages matching participants' reasons for participating were more motivating than mismatched messages. Further, participants preferred messages that were personalized (i.e., use second person voice) and in formal tones. Messages consistent with these preferences were also rated as more motivating. These findings establish the feasibility of using message tailoring to promote adherence to longitudinal protocols and the relevance of tailoring messages to be personal and formal.
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Mitochondrial oxidative stress is one of the characteristics of secondary brain injury (SBI) after intracerebral hemorrhage (ICH), contributing largely to the apoptosis of neurons. Celastrol, a quinone methide triterpene that possesses antioxidant and mitochondrial protective properties, has emerged as a neuroprotective agent. However, the activity of celastrol has not been tested in ICH-induced SBI. In this study, we found that celastrol could effectively alleviate neurological function deficits and reduce brain oedema and neuronal apoptosis caused by ICH. Through electron microscopy, we found that celastrol could significantly attenuate mitochondrial morphology impairment. Therefore, we tested the regulatory proteins of mitochondrial dynamics and found that celastrol could reverse the downwards trend of OPA1 expression after ICH. In view of this, by culturing OPA1-deficient primary neurons and constructing neuron-specific OPA1 conditional knockout mice, we found that the protective effects of celastrol on mitochondrial morphology and function after ICH were counteracted in the absence of OPA1. Further experiments also showed that OPA1 is indispensable for the protective effects of celastrol on ICH-induced secondary brain injury. In summary, we have demonstrated that celastrol is a potential drug for the treatment of ICH and have revealed a novel mechanism by which celastrol exerts its antioxidant effects by promoting OPA1-mediated mitochondrial fusion.
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Lesões Encefálicas , Dinâmica Mitocondrial , Camundongos , Animais , Dinâmica Mitocondrial/fisiologia , Hemorragia Cerebral/metabolismo , Lesões Encefálicas/metabolismo , Antioxidantes/farmacologia , Apoptose , Estresse Oxidativo/fisiologiaRESUMO
Pivotal roles of extracellular vesicles (EVs) in the pathogenesis of central nervous system (CNS) disorders including acute brain injury are increasingly acknowledged. Through the analysis of EVs packaged miRNAs in plasma samples from patients with intracerebral hemorrhage (ICH), it is discovered that the level of EVs packaged miR-143-3p (EVs-miR-143-3p) correlates closely with perihematomal edema and neurological outcomes. Further study reveals that, upon ICH, EVs-miR-143-3p is robustly secreted by astrocytes and can shuttle into brain microvascular endothelial cells (BMECs). Heightened levels of miR-143-3p in BMECs induce the up-regulated expression of cell adhesion molecules (CAMs) that bind to circulating neutrophils and facilitate their transendothelial cell migration (TEM) into brain. Mechanism-wise, miR-143-3p directly targets ATP6V1A, resulting in impaired lysosomal hydrolysis ability and reduced autophagic degradation of CAMs. Importantly, a VCAM-1-targeting EVs system to selectively deliver miR-143-3p inhibitor to pathological BMECs is created, which shows satisfactory therapeutic effects in both ICH and traumatic brain injury (TBI) mouse models. In conclusion, the study highlights the causal role of EVs-miR-143-3p in BMECs' dysfunction in acute brain injury and demonstrates a proof of concept that engineered EVs can be devised as a potentially applicable nucleotide drug delivery system for the treatment of CNS disorders.
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Lesões Encefálicas , Vesículas Extracelulares , MicroRNAs , Humanos , Animais , Camundongos , Células Endoteliais , Migração Transendotelial e Transepitelial , Astrócitos , Neutrófilos , Movimento CelularRESUMO
Reasonable allocation of carbon emission reduction tasks requires addressing household carbon inequality. This study aims to track characteristics of household carbon inequality in China using the recentered influence function (RIF) based on the Household Tracking Survey data in 2018 and the multi-regional input-output table. The Oaxaca-Binder decomposition based on RIF further decomposes household carbon inequality based on spatial heterogeneity into composition and coefficient effects. The results indicate that (1) household carbon inequality is widespread in China, generally close to the 60/30 distribution, favouring high-income families. Furthermore, (2) increases in income, wealth and economic burden and declining marriage rate promote household carbon inequality, which is suppressed by the development of education and the Internet and the increase in car ownership. Additionally, (3) the carbon inequality of urban households is smaller than that of rural households, which is contributed by the composition effects of family size, education, car ownership, Internet development and the coefficient effect of income and housing. Finally, (4) under the composition effect of family size and the coefficient effect of income, the household carbon inequality in the eastern region is smaller than in the central and western regions.
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Características da Família , Renda , Humanos , Fatores Socioeconômicos , China , População Rural , CarbonoRESUMO
Interface engineering attracted tremendous attention owing to its remarkable ability to impede dendrite growth and side reactions in aqueous zinc-ion batteries. Artificial interface layers composed of crystalline materials have been extensively employed to stabilize the Zn anode. However, the diffusion kinetics of Zn2+ in highly crystalline materials are hindered by steric effects from the lattice, thereby limiting the high-rate performance of the cell. Here, defect-rich HfO2-x polycrystals derived from metal-organic frameworks (MOFs) (D-HfO2-x) are developed to enhance the Zn deposition behavior. The discrepancy of dielectric constants between metallic Zn and HfO2 enables the building of an electrostatic shielding layer for uniform Zn deposition. More importantly, the oxygen vacancies in D-HfO2-x provide abundant active sites for Zn2+ adsorption, accelerating the kinetics of Zn2+ migration, which contributes to the preferential exposure of the Zn (002) plane during plating. Consequently, the D-HfO2-x-modified Zn anode delivers ultrastable durability of over 5000 h at 1 mA cm-2 and a low voltage hysteresis of 30 mV. The constructed defective coating provides a guarantee for the stable operation of Zn anodes, and the innovative approach of defective engineering also offers new ideas for the protection of other energy storage devices.
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BACKGROUND AND OBJECTIVES: The future of cognitive assessment is likely to involve mobile applications for smartphones and tablets; cognitive training is also often delivered in these formats. Unfortunately, low adherence to these programs can hinder efforts at the early detection of cognitive decline and interfere with examining cognitive training efficacy in clinical trials. We explored factors that increase adherence to these programs among older adults. RESEARCH DESIGN AND METHODS: Focus groups were conducted with older adults (N = 21) and a younger adult comparison group (N = 21). Data were processed using reflexive thematic analysis with an inductive, bottom-up approach. RESULTS: Three primary themes related to adherence were developed from the focus group data. Switches of engagement reflects factors that must be present; without them, engagement is unlikely. Dials of engagement reflects a cost-benefit analysis that users undergo, the outcome of which determines whether a person will be more or less likely to engage. Bracers of engagement reflects factors that nudge users toward engagement by minimizing barriers associated with the other themes. Older adults in general were more sensitive to opportunity costs, preferred more cooperative interactions, and were more likely to mention technology barriers. DISCUSSION AND IMPLICATIONS: Our results are important for informing the design of mobile cognitive assessment and training apps for older adults. These themes provide guidance about ways apps could be modified to increase engagement and adherence, which in turn can more effectively facilitate the early detection of cognitive impairment and the evaluation of cognitive training efficacy.
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Disfunção Cognitiva , Motivação , Humanos , Idoso , Grupos Focais , Disfunção Cognitiva/diagnóstico , CogniçãoRESUMO
Artificial solid electrolyte interphase in organic solutions is effective and facile for long-cycling aqueous zinc ion batteries. However, the specific effects on different ionic environments have not been thoroughly investigated. Herein, pyromellitic acid (PA) are employed as organic ligand to coordinate with Zn2+ under various ionic environments. The connection between the ionic environment and reaction spontaneity is analyzed to provide insights into the reasons behind the effectiveness of the SEI layer and to characterize its protective impact on the zinc anode. Notably, the PA solution (pH4) lacking OH- contributes to the formation of a dense and ultrathin SEI with Zn-PA coordination, preventing direct contact between the anode and electrolyte. Moreover, the presence of organic functional groups facilitates a uniform flux of Zn2+ . These advantages enable stable cycling of the PA4-Zn symmetric cell at a current density of 3 mA cm-2 for over 3500 h. The PA4-Zn//MVO full cell demonstrates excellent electrochemical reversibility. Investigating the influence of the ionic environment on SEI generation informs the development of novel SEI strategies.
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Transparent objects widely exist in the world. The task of transparent object segmentation is challenging as the object lacks its own texture. The cue of shape information therefore gets more critical. Most existing methods, however, rely on the mechanism of simple convolution, which is good at local cues and performs weakly on global cues like shape. To solve this problem, an operation named Patch-wise Weight Shuffle is proposed to bring in the global context cue by being combined with the dynamic convolution. A network ShuffleTrans that recognizes shape better is then designed based on this operation. Besides, fitter for this task, two auxiliary modules are presented in ShuffleTrans: a Boundary and Direction Refinement Module which collects two additional information, and a Channel Attention Enhancement Module that assists the above operation. Experiments on four texture-less object segmentation datasets and two normal datasets verify the effectiveness and generality of the method. Especially, the ShuffleTrans achieved 74.93% mIoU on the Trans10k v2 test set, which is more accurate than existing methods.
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Sinais (Psicologia) , Processamento de Imagem Assistida por ComputadorRESUMO
OBJECTIVES: Appraisal and interpretation of personal experiences resulting from interaction with situational contexts might play an important role in shaping subjective age at the within-person level, but it is unclear how this process unfolds. We propose that older adults evaluate situational contexts and reflect on their general psychological resources when determining their subjective age, and tested this proposal with volition of daily activities as a proxy for appraisal of situational contexts and control beliefs as a proxy for psychological resources. We hypothesize that appraising daily activities one engaged in as obligatory would deplete one's perceived control and concomitantly make one feel older. METHODS: Older adults (nâ =â 116) ranging in age from 60 to 90 (Mâ =â 64.84) completed a 9-day daily diary study online, resulting in 743 total days. Participants reported their sociodemographic characteristics on Day 1 and major daily activities, volition of every reported activity, felt age, and control beliefs on Days 2-9. RESULTS: On days when older adults felt that activities they engaged in were of their own volition, they also felt more in control. A lower-level mediation result suggested that within-person control beliefs mediated the relationship between volition of daily activities and subjective age. DISCUSSION: Our findings suggest that older adults evaluate situational contexts and reflect on their control beliefs as a general psychological resource when determining their subjective age. These findings show the important role psychological resources play in determining subjective age from a within-person perspective and extended the within-person process proposed in previous theoretical models.
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Envelhecimento , Volição , Humanos , Idoso , Envelhecimento/psicologia , Atividades Cotidianas/psicologia , EmoçõesRESUMO
In recent research, anisotropic plasmonic core-shell nanomaterials have gained a lot of attention in surface-enhanced Raman scattering (SERS) due to their brilliant uniformity and optical properties. Herein, a bimetallic core-molecule-shell (CMS) composite nanorod SERS substrate nanomaterial (Au NB-DT@Ag NRs) was designed and synthesized under precise regulation. The inner core is gold nanobipyramids (Au NBs), which possess superior plasmonic properties. Uniform Au NBs of five different sizes were fabricated via a penta-twinned gold seed mediated growth method. The length varied from 160 to 62 nm and the corresponding diameter varied from 60 to 23 nm while the longitudinal surface plasmonic resonance (SPR) changed from 908 to 715 nm. The SERS activity of five Au NBs were compared and the optimally sized one with a length of 78 nm and width of 28 nm was set as the inner core. After modification with the Raman reporter (DT), different amounts of silver were deposited on the surface of Au NB-DTs to form an Au NB-DT@Ag nanocomposite. The shape of the nanostructure gradually became a rod and lengthened while the longitudinal SPR wavelength varied from 733 nm to 664 nm with an increase in the amount of silver nitrate added. The Au NB-DT@Ag NRs with the best SERS activity (b-3) could realize the quantitative detection of the toxic dyes malachite green (MG) and crystal violet (CV) of concentrations as low as 5 × 10-9 M, showing good reproducibility and stability. This work offers a new design strategy for a SERS substrate for reliable quantitative SERS detection applications.
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Background and Objectives: Sustained computer and internet use have the potential to help older adults in various aspects of their lives, making predicting sustained use a critical goal. However, some factors related to adoption and use (e.g., computer attitudes) change over time and with experience. To understand these dynamics, the current study modeled changes in constructs related to computer use after initial computer adoption and examined whether these changes predict continued use. Research Design and Methods: We used data from the computer arm (N = 150, MAge = 76.15) of a 12-month field trial examining the potential benefits of computer use in older adults. Individual differences identified in the technology acceptance literature (perceived usefulness, ease of use, computer interest, computer self-efficacy, computer anxiety, quality of life, social isolation, and social support) were measured before (baseline), during (Month 6), and after the intervention (post-test). Univariate and bivariate latent change score models examined changes in each predictor and their potential causal relationship with use. Results: Results demonstrated large interindividual differences in the change patterns of individual difference factors examined. Changes in perceived usefulness, perceived ease of use, computer interest, computer self-efficacy, and computer anxiety were correlated with but not predictive of change in use. Discussion and Implications: Our findings demonstrate the limitation of popular constructs in technology acceptance literature in predicting continued use and point out important gaps in knowledge to be targeted in future investigations.
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Diabetic kidney disease (DKD) is one of the common complications of diabetes mellitus, which usually progresses to end-stage renal disease and causes great damage to the health of patients. Endothelin-1 (ET-1), a molecule closely associated with the progression of DKD, has increased expression in response to high glucose stimulation and is involved in hemodynamic changes, inflammation, glomerular and tubular dysfunction in the kidney, causing an increase in proteinuria and a decrease in glomerular filtration function, ultimately leading to glomerulosclerosis and renal failure. This paper aims to review the molecular level changes, regulatory mechanisms, and mechanisms of action of ET-1 under DKD, clinical trials of ET-1 receptor antagonists in recent years and current problems, to provide basic information and new research directions and ideas for the treatment of DKD and ET-1-related research.
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Diabetes Mellitus , Nefropatias Diabéticas , Podócitos , Humanos , Nefropatias Diabéticas/metabolismo , Endotelina-1/genética , Endotelina-1/metabolismo , Podócitos/metabolismo , Glomérulos Renais/metabolismo , Rim/metabolismo , Diabetes Mellitus/metabolismoRESUMO
Background: Both electromagnetic radiation (EMR) and low-frequency noise (LFN) are widespread and influential environmental factors, and operators are inevitably exposed to both EMR and LFN within a complex exposure environment. The potential adverse effects of such exposure on human health must be considered seriously. This study aimed to investigate the effects of EMR and LFN on cognitive function as well as their interaction effect, which remain unclear. Methods: Sixty young male college students were randomly grouped and experiments were conducted with a 2 × 2 factorial design in a shielded chamber. Mental workload (MWL) levels of the study subjects were measured and assessed using the NASA-task load index (TLX) subjective scale, an n-back task paradigm, and the functional near-infrared spectroscopy (fNIRS) imaging technique. Results: For the 3-back task, the NASA-TLX subjective scale revealed a statistically significant main effect of LFN intensity, which enhanced the subjects' MWL level (F = 8.716, p < 0.01). Behavioral performance revealed that EMR intensity (430.1357 MHz, 10.75 W/m2) and LFN intensity (0-200 Hz, 72.9 dB) had a synergistic interaction effect, and the correct response time was statistically significantly prolonged by the combined exposure (F = 4.343, p < 0.05). The fNIRS imaging technique revealed a synergistic interaction effect between operational EMR intensity and operational LFN intensity, with statistically significant effects on the activation levels in the left and right dorsolateral prefrontal cortex (DLPFC). The mean ß values of DLPFC were significantly increased (L-DLPFC F = 5.391, p < 0.05, R-DLPFC F = 4.222, p < 0.05), and the relative concentrations of oxyhemoglobin in the DLPFC were also significantly increased (L-DLPFC F = 4.925, p < 0.05, R-DLPFC F = 9.715, p < 0.01). Conclusion: We found a statistically significant interaction effect between EMR (430.1357 MHz, 10.75 W/m2) and LFN (0-200 Hz, 72.9 dB) when simultaneously exposing subjects to both for 30 min. We conclude that exposure to this complex environment can cause a statistically significant increase in the MWL level of operators, and even alterations in their cognitive function.