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In this work, a photoelectrochemical (PEC) immunosensor was constructed for the ultrasensitive detection of lung cancer marker neuron-specific enolase (NSE) based on a microflower-like heterojunction of cadmium indium sulfide and magnesium indium sulfide (CdIn2S4/MgIn2S4, CMIS) as photoactive material. Specifically, the well-matched energy level structure and narrow energy level gradients between CdIn2S4 and MgIn2S4 could accelerate the separation of electron-hole (e--h+) pairs in the CMIS heterojunction to enhance the photocurrent of CMIS, which was increased 5.5 and 80 times compared with that of single CdIn2S4 and MgIn2S4, respectively. Meanwhile, using CMIS as photoactive material, increasing the biocompatibility by dropping Pt NPs on the surface of CMIS to immobilize the antibody through Pt-N bond. Fe3O4-Ab2, acting as the quencher, competitively consumes electron donors and absorbs light, leading to photocurrent quenching. With the increasing of quencher, the photocurrent decreased. Hence, the developed "signal-off" PEC immunosensor realized the trace detection of NSE within the range from 1.0 fg/mL to 10 ng/mL with a low detection limit of 0.34 fg/mL. This strategy provided a new perspective for establishing ternary metal sulfide heterojunction to construct PEC immunosensor for sensitive detection of disease biomarkers.
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Biomarcadores Tumorais , Índio , Neoplasias Pulmonares , Fosfopiruvato Hidratase , Sulfetos , Humanos , Fosfopiruvato Hidratase/análise , Índio/química , Biomarcadores Tumorais/análise , Sulfetos/química , Limite de Detecção , Técnicas Eletroquímicas , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Compostos de Cádmio/química , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/químicaRESUMO
Progress in histological methods and in microscope technology has enabled dense staining and imaging of axons over large brain volumes, but tracing axons over such volumes requires new computational tools for 3D reconstruction of data acquired from serial sections. We have developed a computational pipeline for automated tracing and volume assembly of densely stained axons imaged over serial sections, which leverages machine learning-based segmentation to enable stitching and alignment with the axon traces themselves. We validated this segmentation-driven approach to volume assembly and alignment of individual axons over centimeter-scale serial sections and show the application of the output traces for analysis of local orientation and for proofreading over aligned volumes. The pipeline is scalable, and combined with recent advances in experimental approaches, should enable new studies of mesoscale connectivity and function over the whole human brain.
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In this study, an ultrasensitive photoelectrochemical (PEC) aptasensor based on dual-sensitized heterojunction Ag2S/ZnS/NiS composites as a signal probe was proposed for the detection of tobramycin (TOB) by combining a cascaded quadratic signal amplification strategy. Specifically, compared to the limited visible light-harvesting capability of single sensitized composites, Ag2S/ZnS/NiS composites with p-n and n-n heterojunction could greatly improve the light energy utilization to tremendously strengthen the optical absorption in the entire visible-light region. Moreover, dual-sensitized heterojunction could effectively hinder the rapid recombination of photoelectrons and holes (carriers) to obtain a good photocurrent for improving the sensitivity of the aptasensor. Furthermore, a cascaded quadratic signal amplification strategy was applied to convert trace target TOB into plentiful gold nanoclusters (Au NCs) labelled double-stranded DNA for the construction of PEC aptasensor, with a broad linear detection range from 0.01 to 100 ng mL-1 and a low detection limit of 3.38 pg mL-1. Importantly, this study provided a versatile and sensitive PEC biosensing platform for TOB analysis, and demonstrated its successful application for TOB detection in milk samples. This protocol provides a novel dual-sensitized heterojunction composites to develop a highly efficient and harmfulless PEC aptasensor, which is expected to be used in food safety, environmental monitoring and other areas.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Técnicas Eletroquímicas , Luz , Limite de Detecção , Leite , Compostos de Prata , Sulfetos , Tobramicina , Compostos de Zinco , Tobramicina/análise , Tobramicina/química , Técnicas Eletroquímicas/métodos , Aptâmeros de Nucleotídeos/química , Compostos de Prata/química , Compostos de Zinco/química , Sulfetos/química , Leite/química , Animais , Nanopartículas Metálicas/química , Antibacterianos/análise , Ouro/química , Contaminação de Alimentos/análiseRESUMO
Cardiac troponin I (cTnI), a protein regulating myocardial contraction, stands the premier biomarker for diagnosing acute myocardial infarction and stratifying heart disease risk. Photoelectrochemical (PEC) biosensing combines traditional PEC analysis with high bioconjugation specificity, rendering a prospective avenue for disease biomarker analysis. However, the performance of sensors often falls short due to inadequate photoelectric materials. Hence, designing heterojunctions with proper band alignment, effective transport and separation of photogenerated carriers is highly expected for PEC sensors. Meanwhile, doping as a synergistic strategy to tune the energy band edges and improve carrier transport in heterojunctions, can also enhance the sensing performance. In this work, bismuth-doped tin oxide and tin disulfide heterojunction (Bi-SnOS) was prepared via a simple one-step hydrothermal method and utilized as a highly sensitive platform. Integrating copper sulfide-coated nano-gold (Au@CuS), a yolk-shell shaped nanocomposites, as the double quenching probe, an excellent PEC biosensor was fabricated to assay cTnI via sandwich immunorecognition. Under optimal conditions, the proposed biosensor displayed a high-performance for cTnI in the range from 0.1 pg/mL to 5.0 ng/mL with a low detection limit (44.7 fg/mL, 3σ). The strong photocurrent response, high stability and suitable selectivity point out that the synergistic effect between heterojunction and doping provides a promising prospect for the design of new PEC materials.
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Técnicas Biossensoriais , Bismuto , Técnicas Eletroquímicas , Nanoestruturas , Compostos de Estanho , Troponina I , Troponina I/análise , Troponina I/sangue , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Bismuto/química , Humanos , Compostos de Estanho/química , Nanoestruturas/química , Processos Fotoquímicos , Limite de Detecção , Ouro/química , Cobre/química , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/químicaRESUMO
Developing multi-functional electrocatalysts is of great practical significance for fuel cells and water splitting. Herein, Rh-Rh2O3 nanoclusters are prepared and the surface oxygen vacancy content is regulated elaborately by post-treatment. The optimized Rh-Rh2O3/C-400 exhibits superior trifunctional catalytic activity for hydrogen oxidation reaction (HOR), hydrogen evolution reaction (HER) and hydrazine oxidation reaction (HzOR), i.e., the mass activity for HOR is 2.29 mA µgRh-1, and the overpotential for HER and HzOR at 10 mA cm-2 is as low as 12 mV and 31 mV, respectively, superior to the benchmark Pt/C. Rh-Rh2O3/C-400 also displays promising performance in practical devices, with the H2-O2 anion-exchange-membrane fuel cell delivering a peak power density of 0.66 W cm-2, and the hydrazine-assisted water splitting electrolyzer requiring a low electrolysis voltage of 0.161 V at 0.1 A cm-2. The experimental and theoretical investigations discover that the hydrogen binding energy (HBE) is linearly depended on surface oxygen vacancy contents, and the HBE directly determines the catalytic activity for HOR, HER and HzOR. This work not only innovates an efficient Rh-based nanocluster tri-functional electrocatalyst, but also eludicates the intrinsic relationship of surface structure-intermediate adsorption-catalytic activity.
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In early sensory systems, cell-type diversity generally increases from the periphery into the brain, resulting in a greater heterogeneity of responses to the same stimuli. Surround suppression is a canonical visual computation that begins within the retina and is found at varying levels across retinal ganglion cell types. Our results show that heterogeneity in the level of surround suppression occurs subcellularly at bipolar cell synapses. Using single-cell electrophysiology and serial block-face scanning electron microscopy, we show that two retinal ganglion cell types exhibit very different levels of surround suppression even though they receive input from the same bipolar cell types. This divergence of the bipolar cell signal occurs through synapse-specific regulation by amacrine cells at the scale of tens of microns. These findings indicate that each synapse of a single bipolar cell can carry a unique visual signal, expanding the number of possible functional channels at the earliest stages of visual processing.
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Retina , Células Ganglionares da Retina , Animais , Camundongos , Células Ganglionares da Retina/fisiologia , Células Amácrinas/fisiologia , Sinapses/fisiologiaRESUMO
Halogenated organic compounds are widespread, and decades of heavy use have resulted in global bioaccumulation and contamination of the environment, including water sources. Here, we introduce the most common halogenated organic water pollutants, their classification by type of halogen (fluorine, chlorine, or bromine), important policies and regulations, main applications, and environmental and human health risks. Remediation techniques are outlined with particular emphasis on carbon-halogen bond strengths. Aqueous advanced redox processes are discussed, highlighting mechanistic details, including electrochemical oxidations and reductions of the water-oxygen system, and thermodynamic potentials, protonation states, and lifetimes of radicals and reactive oxygen species in aqueous electrolytes at different pH conditions. The state of the art of aqueous advanced redox processes for brominated, chlorinated, and fluorinated organic compounds is presented, along with reported mechanisms for aqueous destruction of select PFAS (per- and polyfluoroalkyl substances). Future research directions for aqueous electrocatalytic destruction of organohalogens are identified, emphasizing the crucial need for developing a quantitative mechanistic understanding of degradation pathways, the improvement of analytical detection methods for organohalogens and transient species during advanced redox processes, and the development of new catalysts and processes that are globally scalable.
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Intolerance of uncertainty (IU) is widely considered a transdiagnostic risk and maintaining factor for psychiatric disorders. However, little is known about the overall nature and profile of IU among adolescents. This study aims to investigate the profiles of IU among Chinese adolescents and explore their associations with sociodemographic characteristics and mental health problems. A sample of 108,540 adolescents provided data on IU, sociodemographic characteristics, and mental health via an online platform. Latent profile analysis revealed three profiles: Low IU, Medium IU, and High IU. Girls, older adolescents, and those with specific sociodemographics were more likely to belong to the "High IU" profile. Furthermore, the "High IU" profile was associated with the highest risk of several mental health problems. These findings provided valuable information for early prevention and intervention strategies targeting IU and highlighted the importance of IU-based interventions for mental health among adolescents.
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Seeking and constructing superior photoactive materials have the potential to improve the performance of photoelectrochemical (PEC) biosensors. In this work, we proposed a novel mimosa-like ternary inorganic composite with a significantly enhanced light-harvesting ability and photogenerated carrier separation rate. This ternary photoactive material was obtained via electrodeposition of gold nanoparticles (Au) on the surface of transition metal sulfide composite of CdS and NiS (CdS-NiS/Au). The experimental results showed that the high initial photocurrent was acquired on CdS-NiS/Au (68-fold higher than that of individual CdS) with the synergistic effect of p-n heterojunction, Schottky junction, and the eminent optical properties of gold nanoparticles. Meanwhile, using silver nanoclusters prepared by link DNA protection as an effective quencher, integrating the duplex-specific nuclease-assisted rolling circle amplification strategy, a "Signal ON" PEC biosensor was fabricated for the detection of microRNA 21 (miRNA 21). With the release of the quencher, the recovered photocurrent is able to achieve determination of miRNA 21 within the range from 10 aM to 1 pM with a detection limit down to 4.6 aM (3σ). Importantly, this work not only provides a superb idea for designing ternary inorganic heteromaterials with exceptional photoactive ability but also allows the detection of other biomarkers by selecting appropriate recognition units.
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Técnicas Biossensoriais , Nanopartículas Metálicas , MicroRNAs , Mimosa , Ouro/química , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Limite de DetecçãoRESUMO
We analyzed the enormous scale of global human needs, their carbon footprint, and how they are connected to energy availability. We established that most challenges related to resource security and sustainability can be solved by providing distributed, affordable, and clean energy. Catalyzed chemical transformations powered by renewable electricity are emerging successor technologies that have the potential to replace fossil fuels without sacrificing the wellbeing of humans. We highlighted the technical, economic, and societal advantages and drawbacks of short- to medium-term decarbonization solutions to gauge their practicability, economic feasibility, and likelihood for widespread acceptance on a global scale. We detailed catalysis solutions that enhance sustainability, along with strategies for catalyst and process development, frontiers, challenges, and limitations, and emphasized the need for planetary stewardship. Electrocatalytic processes enable the production of solar fuels and commodity chemicals that address universal issues of the water, energy and food security nexus, clothing, the building sector, heating and cooling, transportation, information and communication technology, chemicals, consumer goods and services, and healthcare, toward providing global resource security and sustainability and enhancing environmental and social justice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11244-023-01799-3.
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Neurons make converging and diverging synaptic connections with distinct partner types. Whether synapses involving separate partners demonstrate similar or distinct structural motifs is not yet well understood. We thus used serial electron microscopy in mouse retina to map output synapses of cone bipolar cells (CBCs) and compare their structural arrangements across bipolar types and postsynaptic partners. Three presynaptic configurations emerge-single-ribbon, ribbonless, and multiribbon synapses. Each CBC type exploits these arrangements in a unique combination, a feature also found among rabbit ON CBCs. Though most synapses are dyads, monads and triads are also seen. Altogether, mouse CBCs exhibit at least six motifs, and each CBC type uses these in a stereotypic pattern. Moreover, synapses between CBCs and particular partner types appear biased toward certain motifs. Our observations reveal synaptic strategies that diversify the output within and across CBC types, potentially shaping the distinct functions of retinal microcircuits.
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Interneurônios , Retina , Animais , Camundongos , Coelhos , Retina/fisiologia , Células Bipolares da Retina , Sinapses , Microscopia EletrônicaRESUMO
Designing photovoltaic materials with good photoelectric activity is the crucial to boost the sensitivity of photoelectrochemical (PEC) biosensors. To meet this concern, a Schottky-functionalized direct Z-scheme heterojunction photovoltaic material was proposed by electrodeposition of gold nanoparticles on two kinds of bismuth oxyhalide composites surface (bismuth oxybromide and bismuth oxyiodide with different but matched band gaps) (depAu/BiOI/BiOBr). Specifically, synergistic effect was achieved through the direct Z-scheme heterojunction formed by BiOBr and BiOI as well as the gold Schottky junction, resulting in the enhanced light harvest and photoelectric conversion efficiency. Meanwhile, combined with sandwich immunotechnology, a "signal-off" PEC biosensor was fabricated for highly sensitive detection of carcinoembryonic antigen (CEA). In which, using depAu/BiOI/BiOBr modified glassy carbon electrodes both as the photoactive sensing interface and capture antibody loading matrix, polyethyleneimine copper complex encapsulated gold nanoclusters labeled detection antibody (Ab2-Au@PEI-Cu) as the quencher, the photocurrent decreased with the increasing target CEA introduced by sandwich immune reaction. The proposed smart PEC immunoassay platform exhibited a wide detection range (1.0 fg/mL-2.0 ng/mL) and a detection limit as low as 0.11 fg/mL with favorable selectivity and stability. In addition, this PEC sensing strategy can be easily extended for other tumor marker analysis, which offers a new perspective of using multiple bismuth oxyhalide as photoactive materials for early diseases diagnosis.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Bismuto , Técnicas Biossensoriais/métodos , Antígeno Carcinoembrionário , Ouro , Técnicas Eletroquímicas/métodos , Limite de Detecção , Imunoensaio/métodosRESUMO
Organic photoelectric materials with conjugated electron-rich structures and good biocompatibilities have broad application prospects in biosensors. Herein, we report a promising organic photoelectric multielectron donor nanocomposite for highly sensitive PEC immunoassays. Specifically, the organic multielectron donor nanocomposite (DA-ZnTCPP-g-C3N4) was prepared from dopamine (DA, polyphenol hydroxyl structure substance), zinc tetracarboxylate porphyrin (ZnTCPP, large p-π conjugated heterocyclic compound), and two-dimensional graphene-like nitrogen carbide (g-C3N4) via an amidation reaction. With a multielectron donor structure and photoelectricity, this nanocomposite can achieve sensitization by self-structure without the addition of an electron donor in the test solution. It was utilized to label the carcinoembryonic detection antibody as a immuno-probe (Ab2-DA-ZnTCPP-g-C3N4). Meanwhile, the glassy carbon electrode electrodeposited with gold nanoparticles anchoring the capture antibody was used as a PEC immunomatrix (Ab1/DpAu/GCE). The enhanced PEC current, "signal on", was confirmed by the immunosensor via sandwich immunorecognition of a carcinoembryonic antigen (CEA). Under optimal conditions, the as-prepared sensing platform displayed high sensitivity for CEA with a dynamic linear response range from 10 fg·mL-1 to 1 mg·mL-1 and a lower detection limit of 3.6 fg·mL-1. This organic nanocomposite showed good sensitivity and stability in an immunosensing system with a low background. This strategy affords a promising approach for biological applications of organic photoelectric materials.
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Técnicas Biossensoriais , Grafite , Nanopartículas Metálicas , Técnicas Biossensoriais/métodos , Ouro/química , Imunoensaio/métodos , Técnicas Eletroquímicas/métodos , Limite de Detecção , Nanopartículas Metálicas/química , Antígeno Carcinoembrionário/química , Grafite/química , AnticorposRESUMO
Optimizing landscape pattern to reduce the risk of non-point source (NPS) pollution is an effective measure to improve river water quality. The "source-sink" landscape theory is a recent research tool for landscape pattern analysis that can effectively integrate landscape type, area, spatial location, and topographic features to depict the spatial heterogeneity of NPS pollution. Based on this theory, we quantitatively analyzed the influence of "source-sink" landscape pattern on the river water quality in one of the most intensive agricultural watersheds in Southeastern China. The results indicated that the proportion of "sink" landscape (68.59%) was greater than that of "source" landscape (31.41%) in the study area. In addition, when elevation and slope increased, the "source" landscape proportion decreased, and the "sink" landscape proportion increased. Nitrogen (N) and phosphorus (P) pollutants in rivers showed significant seasonal and spatial variations. Farmland was the primary source of nitrate nitrogen (NO3--N) and total nitrogen (TN) pollution, whereas residential land was the primary source of ammonium nitrogen (NH4+-N) and total phosphorus (TP) pollution. Intensively cultivated areas and densely inhabited areas degraded water quality despite high proportions of forest land. The four "source-sink" landscape indices (LWLI, LWLI'e, LWLI's, LWLI'd) had significant positive correlations with NO3--N and TN and weak correlations with NH4+-N and TP. The capacity of LWLI to quantify the NPS pollution was greater in agricultural areas than in residential areas. The "source-sink" landscape thresholds resulted in abrupt changes in water quality. When LWLI was â¼0.35, the probability of river water quality degradation increased sharply. The results suggest the importance of optimizing the "source-sink" landscape pattern for mitigating agricultural NPS pollution and provide policy makers with adequate new information on the agroecosystem-environmental interface in highly developed agricultural watersheds.
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Compostos de Amônio , Poluição Difusa , Poluentes Químicos da Água , Nitratos , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Qualidade da Água , Fósforo/análise , Nitrogênio/análiseRESUMO
To reveal the comprehensive impacts of controlled release urea (CRU) on rice production, nitrogen (N) loss, and greenhouse gas (GHG) emissions, a research based on global meta-analysis and machine learning (ML) was conducted. The results revealed that the CRU application instead of conventional fertilizer can increase rice yield, N use efficiency (NUE), and net benefits by 5.24%, 20.18%, and 9.30%, respectively, under the same amount of N. Furthermore, the emission of N2O and CH4, global warming potential (GWP), the loss of N leaching, and NH3 volatilization were respectively reduced by 25.64%, 18.33%, 21.10%, 14.90%, and 35.88%. The enhancing effects of CRU on rice yield and NUE were greater when the nitrogen application rate was 150 kg N ha-1. Nevertheless, the reducing effects of CRU on GHG emission reduction, nitrogen leaching, and NH3 volatilization was greater at high nitrogen application rate (≥150 kg ha-1). Mitigating effects of CRU on N2O and CH4 emission were significant when soil pH ≥ 6, while CRU posed a measurable effect on reducing nitrogen leaching and NH3 volatilization in paddy fields with soil organic carbon lower than 15 g kg-1 and pH lower than 6. Based on the data collected from meta-analysis, the results of ML demonstrated that it was feasible to use soil data and N application rate to predict N losses in rice fields under CRU. The performance of random forest is better than multilayer perceptron regression in predicting N losses from paddy fields. Thus, it is necessary to promote the application of CRU in paddy fields, especially in coarse soil, in which scenario the environmental pollution would be decreased and the rice yields, NUE, and net benefits would be increased. Meanwhile, machine learning models can be used to predict N losses in CRU paddy fields.
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Oryza , Agricultura , Carbono , Preparações de Ação Retardada , Poluição Ambiental , Fertilizantes/análise , Aprendizado de Máquina , Nitrogênio , Óxido Nitroso/análise , Solo , UreiaRESUMO
In the retina, amacrine interneurons inhibit retinal ganglion cell (RGC) dendrites to shape retinal output. Amacrine cells typically use either GABA or glycine to exert synaptic inhibition. Here, we combined transgenic tools with immunohistochemistry, electrophysiology, and 3D electron microscopy to determine the composition and organization of inhibitory synapses across the dendritic arbor of a well-characterized RGC type in the mouse retina: the ON-sustained alpha RGC. We find mixed GABA-glycine receptor synapses across this RGC type, unveiling the existence of "mixed" inhibitory synapses in the retinal circuit. Presynaptic amacrine boutons with dual release sites are apposed to ON-sustained alpha RGC postsynapses. We further reveal the sequence of postsynaptic assembly for these mixed synapses: GABA receptors precede glycine receptors, and a lack of early GABA receptor expression impedes the recruitment of glycine receptors. Together our findings uncover the organization and developmental profile of an additional motif of inhibition in the mammalian retina.
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Glicina/metabolismo , Inibição Neural , Células Ganglionares da Retina/metabolismo , Ácido gama-Aminobutírico/metabolismo , Células Amácrinas/metabolismo , Animais , Dendritos/metabolismo , Regulação para Baixo , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo , Receptores de GABA/metabolismo , Receptores de Glicina/metabolismo , Células Ganglionares da Retina/ultraestrutura , Sinapses/metabolismoRESUMO
BACKGROUND: Aortic root enlargement (ARE) may be an important adjunct to aortic valve replacement (AVR) to prevent patient-prosthesis mismatch and facilitate future valve-in-valve transcatheter AVR (TAVR). However, the early safety and late benefits of adding surgical ARE to AVR remain controversial. METHODS: MEDLINE and EMBASE were searched from 1946 to 2018 for articles comparing patients undergoing AVR+ARE with those undergoing AVR alone. A random-effects meta-analysis was performed to compare early and late clinical outcomes. RESULTS: A total of 2570 AVR+ARE and 5,991 AVR patients were included from 9 observational studies. There was no difference in early mortality (relative risk [RR] 1.21; 95% confidence interval [CI], 0.94-1.54; P = 0.13). Both cardiopulmonary bypass (mean difference [MD] 20 minutes; 95% CI, 15-25; P < 0.01) and aortic cross-clamp time (MD 14 minutes; 95% CI, 11-17, P < 0.01) were higher following AVR+ARE. There was no difference in the risk of permanent pacemaker implantation (RR 1.02; 95% CI, 0.83-1.25; P = 0.86), reoperation for bleeding (RR 1.05; 95% CI, 0.84-1.32; P = 0.64), or stroke (RR 0.93; 95% CI, 0.68-1.27; P = 0.65). The risk of moderate (indexed effective orifice area [iEOA] < 0.85 cm2/m2) and severe (iEOA < 0.65 cm2/m2) patient-prosthesis mismatch (PPM) was lower with AVR+ARE (RR 0.65; 95% CI, 0.51-0.83; P < 0.01) and RR 0.36; 95% CI, 0.16-0.82; P = 0.01, respectively). There was no difference in late mortality (incidence rate ratio [IRR] 1.05; 95% CI, 0.87-1.27; P = 0.59) at mean 7.8-year follow-up in 5 studies. CONCLUSIONS: Surgical ARE is a safe adjunct to AVR in selected patients that does not increase early adverse events and results in less patient-prosthesis mismatch. This strategy allows for a larger valve size at the time of implantation, an important consideration for potential future valve-in-valve procedures in the era of TAVR.
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Aorta Torácica/cirurgia , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter/métodos , Humanos , Desenho de PróteseRESUMO
Ribbon synapses transmit information in sensory systems, but their development is not well understood. To test the hypothesis that ribbon assembly stabilizes nascent synapses, we performed simultaneous time-lapse imaging of fluorescently-tagged ribbons in retinal cone bipolar cells (BCs) and postsynaptic densities (PSD95-FP) of retinal ganglion cells (RGCs). Ribbons and PSD95-FP clusters were more stable when these components colocalized at synapses. However, synapse density on ON-alpha RGCs was unchanged in mice lacking ribbons (ribeye knockout). Wildtype BCs make both ribbon-containing and ribbon-free synapses with these GCs even at maturity. Ribbon assembly and cone BC-RGC synapse maintenance are thus regulated independently. Despite the absence of synaptic ribbons, RGCs continued to respond robustly to light stimuli, although quantitative examination of the responses revealed reduced frequency and contrast sensitivity.
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Células Fotorreceptoras Retinianas Cones/fisiologia , Sinapses/metabolismo , Transmissão Sináptica/fisiologia , Animais , Células Cultivadas , Proteína 4 Homóloga a Disks-Large/genética , Proteína 4 Homóloga a Disks-Large/metabolismo , Microscopia Intravital/métodos , Luz , Proteínas Luminescentes/química , Proteínas Luminescentes/genética , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência/métodos , Estimulação Luminosa , Cultura Primária de Células , Células Bipolares da Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Imagem com Lapso de Tempo/métodos , Proteína Vermelha FluorescenteRESUMO
Choline acetyltransferase (ChAT) expressing retinal amacrine cells are present across vertebrates. These interneurons play important roles in the development of retinal projections to the brain and in motion detection, specifically in generating direction-selective responses to moving stimuli. ChAT amacrine cells typically comprise two spatially segregated populations that form circuits in the 'ON' or 'OFF' synaptic layers of the inner retina. This stereotypic arrangement is also found across the adult human retina, with the notable exception that ChAT expression is evident in the ON but not OFF layer of the fovea, a region specialized for high-acuity vision. We thus investigated whether the human fovea exhibits a developmental path for ON and OFF ChAT cells that is retinal location-specific. Our analysis shows that at each retinal location, human ON and OFF ChAT cells differentiate, form their separate synaptic layers, and establish non-random mosaics at about the same time. However, unlike in the adult fovea, ChAT immunostaining is initially robust in both ON and OFF populations, up until at least mid-gestation. ChAT expression in the OFF layer in the fovea is therefore significantly reduced after mid-gestation. OFF ChAT cells in the human fovea and in the retinal periphery thus follow distinct maturational paths.
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Células Amácrinas/citologia , Neurônios Colinérgicos/citologia , Neurogênese/fisiologia , Células Amácrinas/fisiologia , Animais , Diferenciação Celular/fisiologia , Neurônios Colinérgicos/fisiologia , Feto , Humanos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Sensory processing can be tuned by a neuron's integration area, the types of inputs, and the proportion and number of connections with those inputs. Integration areas often vary topographically to sample space differentially across regions. Here, we highlight two visual circuits in which topographic changes in the postsynaptic retinal ganglion cell (RGC) dendritic territories and their presynaptic bipolar cell (BC) axonal territories are either matched or unmatched. Despite this difference, in both circuits, the proportion of inputs from each BC type, i.e., synaptic convergence between specific BCs and RGCs, remained constant across varying dendritic territory sizes. Furthermore, synapse density between BCs and RGCs was invariant across topography. Our results demonstrate a wiring design, likely engaging homotypic axonal tiling of BCs, that ensures consistency in synaptic convergence between specific BC types onto their target RGCs while enabling independent regulation of pre- and postsynaptic territory sizes and synapse number between cell pairs.