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Switch defective/sucrose nonfermentable (SWI/SNF) complexes are evolutionarily conserved multisubunit machines that play vital roles in chromatin architecture regulation for modulating gene expression via sliding or ejection of nucleosomes in eukaryotes. In plants, perturbations of SWI/SNF subunits often result in severe developmental disorders. However, the subunit composition, pathways of assembly, and genomic targeting of the plant SWI/SNF complexes are poorly understood. Here, we report the organization, genomic targeting, and assembly of 3 distinct SWI/SNF complexes in Arabidopsis thaliana: BRAHMA-Associated SWI/SNF complexes (BAS), SPLAYED-Associated SWI/SNF complexes (SAS), and MINUSCULE-Associated SWI/SNF complexes (MAS). We show that BAS complexes are equivalent to human ncBAF, whereas SAS and MAS complexes evolve in multiple subunits unique to plants, suggesting plant-specific functional evolution of SWI/SNF complexes. We further show overlapping and specific genomic targeting of the 3 plant SWI/SNF complexes on chromatin and reveal that SAS complexes are necessary for the correct genomic localization of the BAS complexes. Finally, we define the role of the core module subunit in the assembly of plant SWI/SNF complexes and highlight that ATPase module subunit is required for global complex stability and the interaction of core module subunits in Arabidopsis SAS and BAS complexes. Together, our work highlights the divergence of SWI/SNF chromatin remodelers during eukaryote evolution and provides a comprehensive landscape for understanding plant SWI/SNF complex organization, assembly, genomic targeting, and function.
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Arabidopsis , Humanos , Arabidopsis/genética , Arabidopsis/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Montagem e Desmontagem da Cromatina/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Cromatina/genética , Cromatina/metabolismo , GenômicaRESUMO
The common pochard (Aythya ferina) is a freshwater diving duck found in the Palearctic region that has been classified as vulnerable by the IUCN due to continuous and rapid population declines across their distribution. To gain a better understanding of its genetic mechanism of adaptive evolution, we successfully sequenced and assembled the first high-quality chromosome-level genome of A. ferina using Illumina, Nanopore and Hi-C sequencing technologies. A total assembly length of 1,130.78 Mbp was obtained, with over 98.81% (1,117.37Mbp) of sequence anchored to 35 pseudo-chromosomes. We predicted 17,232 protein-coding genes, 95.9% of which were functionally annotated. We identified 339 expanded and 937 contracted gene families in the genome of A. ferina, and detected 95 genes that have been positively selected. The significantly enriched Gene Ontology and enriched pathways were related to energy metabolism, immune, nervous, and sensory systems, suggests that these factors likely played an important role in its evolution. Importantly, we recovered signatures of positive selection on genes related to vasoconstriction that may be associated with thermoregulatory adaptations of A. ferina for underwater diving. Overall, the high-quality genome assembly and annotation in this study provides valuable genomic resources for ecological and evolutionary studies, as well as toward the conservation of A. ferina.
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Mergulho , Patos , Evolução Molecular , Genoma , Animais , Patos/genética , Cromossomos/genética , Adaptação Fisiológica/genética , Anotação de Sequência Molecular , Genômica/métodos , Seleção GenéticaRESUMO
C3H6 is a crucial building block for many chemicals, yet separating it from other C3 hydrocarbons presents a significant challenge. Herein, we report a hydrolytically stable Cu4I4-triazolate metal-organic framework (MOF) (JNU-9-CH3) featuring 1D channels decorated with readily accessible iodine and nitrogen atoms from Cu4I4 clusters and triazolate linkers, respectively. The exposed iodine and nitrogen atoms allow for cooperative binding of C3 hydrocarbons, as evidenced by in situ single-crystal crystallography and Raman spectroscopy studies. As a result, JNU-9-CH3 exhibits substantially stronger binding affinity for C3H4, CH2âCâCH2, and C3H8 than that for C3H6. Breakthrough experiments confirm its ability to directly separate C3H6 (≥99.99%) from C3H4/CH2âCâCH2/C3H8/C3H6 mixtures at varying ratios and flow rates. Overall, we illustrate the cooperative binding of C3 hydrocarbons in a Cu4I4-triazolate MOF and its highly efficient C3H6 purification from quaternary C3 mixtures. The study highlights the potential of MOF adsorbents with metal-iodide clusters for cooperative bindings and hydrocarbon separations.
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Manipulating single electrons at the atomic scale is vital for mastering complex surface processes governed by the transfer of individual electrons. Polarons, composed of electrons stabilized by electron-phonon coupling, offer a pivotal medium for such manipulation. Here, using scanning tunneling microscopy and spectroscopy (STM/STS) and density functional theory (DFT) calculations, we report the identification and manipulation of a new type of polaron, dubbed van der Waals (vdW) polaron, within mono- to trilayer ultrathin films composed of Sb2O3 molecules that are bonded via vdW attractions. The Sb2O3 films were grown on a graphene-covered SiC(0001) substrate via molecular beam epitaxy. Unlike prior molecular polarons, STM imaging observed polarons at the interstitial sites of the molecular film, presenting unique electronic states and localized band bending. DFT calculations revealed the lowest conduction band as an intermolecular bonding state, capable of ensnaring an extra electron through locally diminished intermolecular distances, thereby forming an intermolecular vdW polaron. We also demonstrated the ability to generate, move, and erase such vdW polarons using an STM tip. Our work uncovers a new type of polaron stabilized by coupling with intermolecular vibrations where vdW interactions dominate, paving the way for designing atomic-scale electron transfer processes and enabling precise tailoring of electron-related properties and functionalities.
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Microbial pigments play a significant role in glacier albedo reduction, thereby contributing to accelerated glacier retreat. The Tibetan Plateau has experienced rapid glacier retreat in recent decades due to global warming, yet there is limited understanding of microbial pigment distribution in the region. Here, we investigated the pigment concentration and composition in cryoconite from four glaciers. Our results showed that chlorophylls were the dominant pigments in Palong No. 4 (PL) and Jiemayangzong (JMYZ) glaciers located in the south of the Tibetan Plateau, while carotenoids were dominant in Qiangyong (QY) and Tanggula (TGL) glaciers located in the central region. Additionally, the chlorophyll b to chlorophyll a ratio, which is an indicator of the algae-to-cyanobacteria ratio, was higher in PL and JMYZ compared to QY and TGL. By using Random Forest Regression and Structural Equation Modelling, we determined that the concentrations of chlorophyll a, chlorophyll b, and carotenoids were associated with autotrophic bacteria relative abundance, climatic factors, and a combination of bacterial and climatic factors, respectively. This study is the first to describe the distribution of microbial pigments in cryoconite from Tibetan glaciers, providing additional support on the influence of algal pigment on glacier retreat.
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Cianobactérias , Camada de Gelo , Camada de Gelo/microbiologia , Tibet , Clorofila A , CarotenoidesRESUMO
Combined in situ analysis of oceanic CO2 concentrations and diverse C and O isotope characteristics can offer a unique perspective with multiple isotopic tracing dimensions for identifying marine biogeochemical processes. Applying this strategy in marine environments is urgently required, yet it faces inherent challenges in terms of existing analytical methods and instruments, e.g., a lack of in situ sensors, limited detectable isotope variety, and low-temporal-resolution data. Here, we report an underwater in situ dissolved CO2 isotope sensor based on mid-infrared tunable diode laser absorption spectroscopy (MIR-TDLAS) and membrane extraction technology. Through the proposed targeted strategies, the sensor is capable of providing high-temporal-resolution in situ measurement of all monosubstituted isotopes of dissolved CO2 (16O13C16O, 18O12C16O, and 17O12C16O) at marine background concentrations. The sensor is demonstrated to provide comparable precision to that of isotope ratio mass spectrometry. At 400 ppmv, the precision for R13C, R18O, and R17O could achieve 0.084, 0.042, and 0.013, respectively, for a 1 s integration time. By enabling a high-frequency in situ analysis in fixed-point time-series field deployment, a 17O anomaly with strong regularity is observed, which is not obvious in 18O and 13C, and therefore, the superiority of the proposed multidimensional in situ isotope tracing strategy is demonstrated. The developed sensor has great potential to open up new prospects for advancing marine carbon research.
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The limited ionic conductivity and unstable interface due to poor solid-solid interface pose significant challenges to the stable cycling of solid-state batteries (SSBs). Herein, an interfacial plasticization strategy is proposed by introducing a succinonitrile (SN)-based plastic curing agent into the polyacrylonitrile (PAN)-based composite polymer electrolytes (CPE) interface. The SN at the interface strongly plasticizes the PAN in the CPE, which reduces the crystallinity of the PAN drastically and enables the CPE to obtain a low modulus surface, but it still maintains a high modulus internally. The reduced crystallinity of PAN provides more amorphous regions, which are favorable for Li+ transport. The gradient modulus structure not only ensures intimate interfacial contact but also favors the suppression of Li dendrites growth. Consequently, the interfacial plasticized CPE (SF-CPE) obtains a high ionic conductivity of 4.8 × 10-4 S cm-1 as well as a high Li+ transference number of 0.61. The Li-Li symmetric cell with SF-CPE can cycle for 1000 h at 0.1 mA cm-2, the LiFeO4 (LFP)-Li full-cell demonstrates a high capacity retention of 86.1% after 1000 cycles at 1 C, and the LiCoO2 (LCO)-Li system also exhibits an excellent cycling performance. This work provides a novel strategy for long-life solid-state batteries.
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Copper (Cu) is an essential micronutrient for all living organisms but is also highly toxic in excess. Cellular homoeostasis of Cu is maintained by various transporters and metallochaperones. Here, we investigated the biological function of OsCOPT7, a member of the copper transporters (COPT) family, in Cu homoeostasis in rice. OsCOPT7 was mainly expressed in the roots and the expression was upregulated by Cu deficiency. OsCOPT7 was localized at the tonoplast and the endoplasmic reticulum. Knockout of OsCOPT7 increased Cu accumulation in the roots but decreased Cu concentrations in the shoots and grain. The knockout mutants contained higher concentrations of Cu in the roots cell sap but markedly lower concentrations of Cu in the xylem sap than wild-type plants. Seed setting and grain yield were reduced significantly in the knockout mutants grown in a low Cu soil. Knockout mutants were more tolerant to Cu toxicity. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that OsCOPT7 interacts physically with the rice Cu chaperone antioxidant protein 1 (OsATX1). Taken together, our results indicate that OsCOPT7 is a specific Cu transporter functioning to export Cu from the vacuoles and the ER and plays an important role in controlling the root-to-shoot Cu translocation in rice.
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Cobre , Retículo Endoplasmático , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Transporte Biológico , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/genética , Cobre/metabolismo , Grão Comestível/metabolismo , Grão Comestível/genética , Retículo Endoplasmático/metabolismo , Técnicas de Inativação de Genes , Oryza/metabolismo , Oryza/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Sementes/metabolismo , Sementes/genética , Vacúolos/metabolismoRESUMO
Ultraviolet micro-LEDs show great potential as a light source for maskless photolithography. However, there are few reports on micro-LED based maskless photolithography systems, and the studies on the effects of system parameters on exposure patterns are still lacking. Hence, we developed a maskless photolithography system that employs micro-LEDs with peak wavelength 375â nm to produce micrometer-sized exposure patterns in photoresists. We also systematically explored the effects of exposure time and current density of micro-LED on static direct writing patterns, as well as the effects of stage velocity and current pulse width on dynamic direct writing patterns. Furthermore, reducing the size of micro-LED pixels enables obtaining high-resolution exposure patterns, but this approach will bring technical challenges and high costs. Therefore, this paper proposes an oblique direct writing method that, instead of reducing the micro-LED pixel size, improves the pattern resolution by changing the tilt angle of the sample. The experimental results show that the linewidths of the exposed lines decreased by 4.0% and 15.2%, respectively, as the sample tilt angle increased from 0° to 15° and 30°, which confirms the feasibility of the proposed method to improve the pattern resolution. This method is also expected to correct the exposure pattern error caused by optical distortion of the lens in the photolithography system. The system and method reported can be applied in various fields such as PCBs, photovoltaics, solar cells, and MEMS.
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BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and is associated with considerable morbidity and mortality. Ischaemic heart failure (IHF) remains one of the most common causes of AF in clinical practice. However, ischaemia-mediated mechanisms leading to AF are still incompletely understood, and thus, current treatment approaches are limited. To improve our understanding of the pathophysiology, we studied a porcine IHF model. METHODS: In pigs, IHF was induced by balloon occlusion of the left anterior descending artery for 90 min. After 30 days of reperfusion, invasive haemodynamic measurements and electrophysiological studies were performed. Masson trichrome and immunofluorescence staining were conducted to assess interstitial fibrosis and myofibroblast activation in different heart regions. RESULTS: After 30 days of reperfusion, heart failure with significantly reduced ejection fraction (left anterior obique 30°, 34.78 ± 3.29% [IHF] vs. 62.03 ± 2.36% [control], p < .001; anterior-posterior 0°, 29.16 ± 3.61% vs. 59.54 ± 1.09%, p < .01) was observed. These pigs showed a significantly higher susceptibility to AF (33.90% [IHF] vs. 12.98% [control], p < .05). Histological assessment revealed aggravated fibrosis in atrial appendages but not in atrial free walls in IHF pigs (11.13 ± 1.44% vs. 5.99 ± .86%, p < .01 [LAA], 8.28 ± .56% vs. 6.01 ± .35%, p < .01 [RAA]), which was paralleled by enhanced myofibroblast activation (12.09 ± .65% vs. 9.00 ± .94%, p < .05 [LAA], 14.37 ± .60% vs. 10.30 ± 1.41%, p < .05 [RAA]). Correlation analysis indicated that not fibrosis per se but its cross-regional heterogeneous distribution across the left atrium was associated with AF susceptibility (r = .6344, p < .01). CONCLUSION: Our results suggest that left atrial cross-regional fibrosis difference rather than overall fibrosis level is associated with IHF-related AF susceptibility, presumably by establishing local conduction disturbances and heterogeneity.
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Fibrilação Atrial , Insuficiência Cardíaca , Suínos , Animais , Fibrilação Atrial/complicações , Átrios do Coração/patologia , Fibrose , IsquemiaRESUMO
PURPOSE: Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications. METHOD: A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [64Cu]Cu-CB-TE2A-iPA-NRA ([64Cu]Cu-4a-c, i = 1, 2, 3), [64Cu]Cu-NOTA-2PA-NRA ([64Cu]Cu-4d), [64Cu]Cu-DOTA-2PA-NRA ([64Cu]Cu-4e, also known as [64Cu]Cu-3BP-227), and [64Cu]Cu-DOTA-VS-2PA-NRA ([64Cu]Cu-4f). The series of small animal PET/CT were conducted in H1299 lung cancer model. The expression profile of NTSR1 was also confirmed by IHC using patient tissue samples. RESULTS: For most of the compounds studied, PET/CT showed prominent tumor uptake and high tumor-to-background contrast, but the tumor retention was strongly influenced by the chelators used. For previously reported 4e, [64Cu]Cu-labeled derivative showed initial high tumor uptake accompanied by rapid tumor washout at 24 h. The newly developed [64Cu]Cu-4d and [64Cu]Cu-4f demonstrated good tumor uptake and tumor-to-background contrast at early time points, but were less promising in tumor retention. In contrast, our lead compound [64Cu]Cu-4b demonstrated 9.57 ± 1.35, 9.44 ± 2.38 and 9.72 ± 4.89%ID/g tumor uptake at 4, 24, and 48 h p.i., respectively. Moderate liver uptake (11.97 ± 3.85, 9.80 ± 3.63, and 7.72 ± 4.68%ID/g at 4, 24, and 48 h p.i.) was observed with low uptake in most other organs. The PA linker was found to have a significant effect on drug distribution. Compared to [64Cu]Cu-4b, [64Cu]Cu-4a had a lower background, including a greatly reduced liver uptake, while the tumor uptake was only moderately reduced. Meanwhile, [64Cu]Cu-4c showed increased uptake in both the tumor and the liver. The clinical relevance of NTSR1 was also demonstrated by the elevated tumor expression in patient tissue samples. CONCLUSIONS: Through the side-by-side comparison, [64Cu]Cu-4b was identified as the lead agent for further evaluation based on its high and sustained tumor uptake and moderate liver uptake. It can not only be used to efficiently detect NTSR1 expression in lung cancer (for diagnosis, patient screening, and treatment monitoring), but also has the great potential to treat NTSR-positive lesions once chelating to the beta emitter 67Cu.
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Quelantes , Radioisótopos de Cobre , Compostos Radiofarmacêuticos , Receptores de Neurotensina , Animais , Receptores de Neurotensina/metabolismo , Camundongos , Quelantes/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/química , Distribuição Tecidual , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Marcação por IsótopoRESUMO
Lipid droplets (LDs) are subcellular organelles that are dynamic and play a central role in energy homeostasis and lipid metabolism. They also contribute to the transport and maturation of cellular proteins and are closely associated with several diseases. The important role of the cellular microenvironment in maintaining cellular homeostasis. Changes in cell polarity, particularly in organelles, have been found to be strongly linked to inflammation, Alzheimer's disease, cancer, and other illnesses. It is essential to check the polarity of the LDs. A series of arylated naphthalimide derivatives were synthesized using the Suzuki reaction. Modification of synthesized aryl naphthalimides using oligomeric PEG based on intramolecular charge transfer (ICT) mechanism. A series of fluorescent probes were designed to target LDs and detect their polarity. Nap-TPA-PEG3 probe exhibited high sensitivity to polarity. The addition of oligomeric polyethylene glycol (PEG) to the probe not only significantly improved its solubility in water, but also effectively reduced its cytotoxicity. In addition, the probe exhibited excellent aggregation-induced luminescence (AIE) properties and solvent discolouration effects. Nap-TPA-PEG3 probe exhibited high Pearson correlation coefficient (0.957163) in lipid droplet co-localization in cells. Nap-TPA-PEG3 could be used as an effective hand tool to monitor cell polarity.
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Corantes Fluorescentes , Gotículas Lipídicas , Naftalimidas , Polietilenoglicóis , Corantes Fluorescentes/química , Humanos , Polietilenoglicóis/química , Gotículas Lipídicas/química , Naftalimidas/química , Polaridade Celular , Células HeLaRESUMO
OBJECTIVE: Lifestyle factors after cancer diagnosis could influence cancer survival. This study aimed to investigate the joint effects of smoking, physical activity, alcohol consumption, diet and sleep duration on all-cause, cancer and non-cancer mortality of cancer survivors in UK biobank. METHODS: The follow-up period concluded in December 2021, with post-diagnostic lifestyle factors assessed at baseline. A lifestyle score ranging from 0 to 5 was assigned based on adherence to the selected lifestyle factors. The study employed Cox regression models for hazard ratios (HRs) and Kaplan-Meier for survival rates, with stratified and sensitivity analyses to assess the robustness of our findings under various assumptions. RESULTS: During a median follow-up of 12.7 years, 5652 deaths were documented from 34,184 cancer survivors. Compared to scoring 0-1, the HRs (95% CIs) for all-cause mortality with lifestyle scores of 2, 3, 4, and 5 were 0.70 (95% CI: 0.64, 0.76), 0.57 (0.52, 0.62), 0.50 (0.45, 0.54) and 0.43 (0.38, 0.48), respectively. Specific cancer types, particularly digestive, breast, female reproductive, non-solid, and skin cancers, showed notable benefits from adherence to healthy lifestyle, with the HRs of 0.55 (0.39, 0.79), 0.54 (0.42, 0.70), 0.32 (0.19, 0.53), 0.58 (0.39, 0.86), and 0.36 (0.28, 0.46) for lifestyle score of 5, respectively. Stratified analyses indicated the association was particularly significant among those with normal/lower BMI and higher Townsend Deprivation Index (Pinteraction = 0.001 and < 0.001, respectively). CONCLUSIONS: Healthier lifestyles were significantly linked with reduced mortality among cancer survivors. These findings highlight the need for adherence to healthy lifestyle habits to improve survival.
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Consumo de Bebidas Alcoólicas , Sobreviventes de Câncer , Exercício Físico , Estilo de Vida , Neoplasias , Humanos , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias/mortalidade , Reino Unido/epidemiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Idoso , Fumar/epidemiologia , Dieta , Adulto , Modelos de Riscos ProporcionaisRESUMO
Glacial lake ecosystems are experiencing rapid changes due to accelerated glacier retreat. As glaciers recede, their influence on downstream habitats diminishes, potentially affecting the biodiversity of glacial lake microbial communities. However, there remains a knowledge gap regarding how bacterial biodiversity patterns in glacial lakes are altered by diminishing glacial influence. Here, we investigated shifts in bacterial communities in paired water and sediment samples collected from seven glacial lakes on the Tibetan Plateau, using a space-for-time substitution approach to understand the consequences of glacier retreat. Our findings reveal that bacterial diversity in lake water increases significantly with a higher glacier index (GI), whereas sediment bacterial diversity exhibits a negative correlation with GI. Both the water and sediment bacterial communities display significant structural shifts along the GI gradient. Notably, reduced glacial influence decreases the complexity of bacterial co-occurrence networks in lake water but enhances the network complexity in sediment. This divergence in diversity and co-occurrence patterns highlights that water and sediment bacterial communities respond differently to changes in glacial influence in these lake ecosystems. This study provides insights into how diminishing glacial influence impacts the bacterial biodiversity in glacial lake water and sediments, revealing contrasting patterns between the two habitats. These findings emphasize the need for comprehensive monitoring to understand the implications of glacier retreat on these fragile ecosystems.
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Bactérias , Biodiversidade , Sedimentos Geológicos , Camada de Gelo , Lagos , Lagos/microbiologia , Sedimentos Geológicos/microbiologia , Camada de Gelo/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Microbiota , Ecossistema , Tibet , RNA Ribossômico 16S/genética , Microbiologia da ÁguaRESUMO
Sliding grating-structured triboelectric nanogenerators (SG-TENGs) can multiply transferred charge, reduce open-circuit voltage, and increase short-circuit current, which have wide application prospects in self-powered systems. However, conventional SG-TENGs have an ultrahigh internal equivalent impedance, which reduces the output voltage and energy under low load resistances (<10 MΩ). The Pulsed SG-TENGs can reduce the equivalent impedance to near zero by introducing a synchronously triggered mechanical switch (STMS), but its limited output time causes the incomplete charge transfer under high load resistances (>1 GΩ). In this paper, a conventional and pulsed hybrid SG-TENG (CPH-SG-TENG) is developed through rational designing STMS with tunable width and output time. The matching relationship among grid electrode width, contactor width of STMS, sliding speed, and load resistance has been studied, which provides a feasible solution for simultaneous realization of high output energy under small load resistances and high output voltage under high load resistances. The impedance matching range is extended from zero to at least 10 GΩ. The output performance of CPH-SG-TENG under low and high load resistances are demonstrated by passive power management circuit and arc discharge, respectively. The general strategy using tunable STMS combines the advantages of conventional and pulsed TENGs, which has broad application prospects in the fields of TENGs and self-powered systems.
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BACKGROUND: Traumatic hemorrhagic shock (THS) is a complex pathophysiological process resulting in multiple organ failure. Intestinal barrier dysfunction is one of the mechanisms implicated in multiple organ failure. The present study aimed to explore the regulatory role of mitogen-activated protein kinase kinase 3 (MKK3) in THS-induced intestinal injury and to elucidate its potential mechanism. METHODS: Rats were subjected to trauma and hemorrhage to establish a THS animal model. MKK3-targeted lentiviral vectors were injected via the tail vein 72 h before modeling. Twelve hours post-modeling, the mean arterial pressure (MAP) and heart rate (HR) were monitored, and histological injury to the intestine was assessed via H&E staining and transmission electron microscopy. Mitochondrial function and mitochondrial reactive oxygen species (ROS) were evaluated. IEC-6 cells were exposed to hypoxia to mimic intestinal injury following THS in vitro. RESULTS: MKK3 deficiency alleviated intestinal injury and restored mitochondrial function in intestinal tissues from THS-induced rats and hypoxia-treated IEC-6 cells. In addition, MKK3 deficiency promoted Sirt1/PGC-1α-mediated mitochondrial biogenesis and restricted Pink1/Parkin-mediated mitophagy in the injured intestine and IEC-6 cells. Furthermore, the protective effect of MKK3 knockdown against hypoxia-induced mitochondrial damage was strengthened upon simultaneous LC3B/Pink1/Parkin knockdown or weakened upon simultaneous Sirt1 knockdown. CONCLUSION: MKK3 deficiency protected against intestinal injury induced by THS by promoting mitochondrial biogenesis and restricting excessive mitophagy.
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Intestinos , MAP Quinase Quinase 3 , Mitocôndrias , Espécies Reativas de Oxigênio , Choque Hemorrágico , Animais , Masculino , Ratos , Linhagem Celular , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/patologia , MAP Quinase Quinase 3/metabolismo , MAP Quinase Quinase 3/genética , Mitocôndrias/metabolismo , Mitofagia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Choque Hemorrágico/complicações , Choque Hemorrágico/metabolismo , Choque Hemorrágico/genética , Choque Traumático/metabolismo , Choque Traumático/complicações , Choque Traumático/genéticaRESUMO
Inhibiting mesangial cell proliferation is one of the strategies to control the early progression of diabetic nephropathy (DN). GSK3ß is closely related to cell apoptosis as well as the development of DN, but whether it acts on the proliferation of mesangial cells is unclear. This study aimed to elucidate the role and mechanism of GSK3ß-mediated lncRNA in high glucose-induced mesangial cell proliferation. HBZY-1 cells were used to establish the cell model of DN. The automatic cell counter was applied to assess cell proliferation. Flow cytometry was used to detect cell apoptosis and intracellular ROS levels. High-throughput transcriptomics sequencing was performed to detect the different expressions of long noncoding RNAs (lncRNAs) in the cell model of DN after knocking down the expression of GSK3ß by the transfection of siRNA. The expression of RNA was detected by real-time PCR. In the cell model of DN using HBZY-1 cells, cell proliferation was enhanced accompanied by GSK3ß activation and elevated apoptosis rate and reactive oxygen species (ROS) levels. A panel of novel lncRNAs, which were differentially expressed after GSK3ß knockdown in the cell model of DN, were identified by high-throughput transcriptomics sequencing. Among them, the expression of TCONS_00071187 was upregulated under high glucose conditions while the knockdown of the GSK3ß expression led to the downregulation of TCONS_00071187. The knockdown of TCONS_00071187 resulted in reduced mesangial cell proliferation, and decreased apoptosis rates and ROS levels. In conclusion, GSK3ß promoted mesangial cell proliferation by upregulating TCONS_00071187, which led to enhanced ROS production under high glucose conditions in the cell model of DN. This study revealed the role of GSK3ß medicated lncRNAs in the development of DN.
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Diabetes Mellitus , Nefropatias Diabéticas , Glicogênio Sintase Quinase 3 beta , RNA Longo não Codificante , Proliferação de Células/genética , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Glucose/toxicidade , Glicogênio Sintase Quinase 3 beta/genética , Espécies Reativas de Oxigênio , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , RatosRESUMO
The commercial applications of lead halide perovskites are hindered by their negative environmental impact and inherent instability. Consequently, developing environmentally friendly copper-based perovskite materials is crucial for future solid-state lighting and display applications. In this study, an ultrafast high-power ultrasonic synthesis strategy was utilized to achieve uniform nucleation and growth of Cs3Cu2X5 (X = Cl, Br, I) nanocrystals (NCs) that possess remarkable luminescence properties, hydroxyl protection, and ligand-free characteristics. These Cs3Cu2X5 NCs exhibited a tunable spectral range spanning from 446 to 525 nm, accompanied by photoluminescence quantum yields (PLQYs) varying from 0.2% to 79.2%. The spectral attributes of the NCs were effectively controlled by modulating the halide type and composition. It is worth noting that density functional theory (DFT) calculations offer valuable insights into the synthesis of NCs and the selection of suitable alcohol solvents. Moreover, we successfully fabricated an efficient and stable white light-emitting diode (WLED) with a high luminous efficiency of 23 lm W-1 and CIE color coordinates of (0.3266, 0.3487). Our work provides a new strategy to synthesize Cs3Cu2X5 NCs and holds promise for their potential application in display and lighting devices.
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Team-based physical activity (PA) can improve social cognition; however, few studies have investigated the neurobiological mechanism underlying this benefit. Accordingly, a hyper-scanning protocol aimed to determine whether the interbrain synchrony (IBS) is influenced by an acute bout of team-based PA (i.e., tandem rope skipping). Specifically, we had socially avoidant participants (SOA, N=15 dyads) and their age-matched controls (CO, N=16 dyads) performed a computer-based cooperative task while EEG was recorded before and after two different experimental conditions (i.e., 30-min of team-based PA versus sitting). Phase locking value (PLV) was used to measure IBS. Results showed improved frontal gamma band IBS after the team-based PA compared to sitting when participants received successful feedback in the task (Mskipping = 0.016, Msittting = -0.009, p = 0.082, ηp2 = 0.387). The CO group showed a larger change in frontal and central gamma band IBS when provided failure feedback in the task (Mskipping = 0.017, Msittting = -0.009, p = 0.075, ηp2 = 0.313). Thus, results suggest that socially avoidant individuals may benefit from team-based PA via improved interbrain synchrony. Moreover, our findings deepen our understanding of the neurobiological mechanism by which team-based PA may improve social cognition among individuals with or without social avoidance.
Assuntos
Eletroencefalografia , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Eletroencefalografia/métodos , Exercício Físico/fisiologia , Cognição Social , Amigos , Comportamento Cooperativo , Ritmo Gama/fisiologia , Encéfalo/fisiologiaRESUMO
BACKGROUND: Blood lipid profiles are associated with various nutritional elements and dietary factors. This study aimed to explore the association between total dietary vitamin E intake and remnant cholesterol (RC), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: A cross-sectional analysis was conducted using NHANES 2007-2018 data. A total of 8,639 eligible participants (45.58% men and 54.42% women) with an average age of 46.12 ± 16.65 years were included in this study. Weighted multivariate linear regression and subgroup analyses were used to examine the association between vitamin E intake and RC, TC, HDL-C, and LDL-C. Smooth curve fitting was used to explore potential non-linear associations. RESULTS: After adjusting for other covariates, multivariate linear regression analysis showed that higher vitamin E intake was negatively associated with plasma RC (ß = -0.22, 95% CI: -0.27, -0.16), TC (ß = -0.33, 95% CI: -0.51, -0.16), LDL-C (ß = -0.25, 95% [confidence interval] CI: -0.40, -0.10) and positively associated with HDL-C (ß = 0.13, 95% CI: 0.07, 0.20) in US adults. Subgroup analysis indicated that age may influence the association between vitamin E intake and RC. At the same time, gender may also affect the association between vitamin E intake and HDL-C. CONCLUSION: Higher vitamin E intake was negatively associated with plasma RC, TC, LDL-C and positively associated with HDL-C.