Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 101
Filtrar
1.
Cereb Cortex ; 34(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38602739

RESUMEN

Non-invasive brain stimulations have drawn attention in remediating memory decline in older adults. However, it remains unclear regarding the cognitive and neural mechanisms underpinning the neurostimulation effects on memory rehabilitation. We evaluated the intervention effects of 2-weeks of neurostimulations (high-definition transcranial direct current stimulation, HD-tDCS, and electroacupuncture, EA versus controls, CN) on brain activities and functional connectivity during a working memory task in normally cognitive older adults (age 60+, n = 60). Results showed that HD-tDCS and EA significantly improved the cognitive performance, potentiated the brain activities of overlapping neural substrates (i.e. hippocampus, dlPFC, and lingual gyrus) associated with explicit and implicit memory, and modulated the nodal topological properties and brain modular interactions manifesting as increased intramodular connection of the limbic-system dominated network, decreased intramodular connection of default-mode-like network, as well as stronger intermodular connection between frontal-dominated network and limbic-system-dominated network. Predictive model further identified the neuro-behavioral association between modular connections and working memory. This preliminary study provides evidence that noninvasive neurostimulations can improve older adults' working memory through potentiating the brain activity of working memory-related areas and mediating the modular interactions of related brain networks. These findings have important implication for remediating older adults' working memory and cognitive declines.


Asunto(s)
Memoria a Corto Plazo , Estimulación Transcraneal de Corriente Directa , Vida Independiente , Encéfalo/diagnóstico por imagen , Sistema Límbico
2.
Appl Opt ; 63(6): A32-A43, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38437355

RESUMEN

A pulse laser with a wavelength of 1064 nm and a pulse width of 1 µs was used to experiment on the coating of a 2024 aluminum alloy surface. The removal performance of the pulse laser cleaning coating was explored by a single factor analysis and orthogonally conditions, and the effects of the laser power, scanning speed, and pulse frequency on the quality of laser coating removal were summarized. The mechanisms of pulse laser cleaning the coating were studied. The results show that the three parameters of the laser power, scanning speed, and pulse frequency have different effects on the quality of laser coating removal. Among them, with the increase of the scanning speed and pulse frequency, the quality of laser cleaning first increases and then decreases, respectively. With the increase in laser power, the quality of laser cleaning increases. A good laser cleaning quality can be achieved at the laser power of 16.5 W, a scanning speed of 600 mm/s, and a pulse frequency of 30 kHz. The laser cleaning coating involves a variety of mechanisms such as combustion, explosion, gasification, thermal vibration stripping, and laser plasma impact. The result can provide practical references for a better searching of the paint removal.

3.
ACS Appl Mater Interfaces ; 16(11): 14198-14207, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38456671

RESUMEN

Materials with low ice adhesion and long-lasting anti-icing properties remain an ongoing challenge in ultralow temperature environments (≤-30 °C). This study presents a gel material consisting of a polymer matrix (copolymer of polyurethane and acrylamide) and an anti-icing agent, ethylene glycol (EG), designed for anti-icing applications at ultralow temperatures. The surface shows a prolonged droplet freezing delay of ca. 322 s at -30 °C and frost resistance properties. It also exhibits an ice adhesion strength of 1.1 kPa at -10 °C and 39.8 kPa at -50 °C, resulting from the interaction between EG and water molecules that hinders the crystallization of ice as well as the significant mismatch between elastic gel and ice. In addition, the gel surface exhibits favorable anti-icing durability, with an ice adhesion strength below 20.0 kPa after 25 icing/deicing cycles and mechanical scratch tests. The gel demonstrates remarkable thermal durability, achieved through the H-bonds between the EG and polymer matrix. The H-bonds further enhance the anti-icing performance, thereby remarkably decreasing EG depletion and improving anti-icing durability. Overall, these properties suggest the potential application of this gel material in harsh environments including polar regions.

4.
ACS Omega ; 9(4): 4931-4948, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38313483

RESUMEN

Pneumatic conveying devices are commonly used in the fields of chemical industry, raw material transportation, and material processing. Elongated biomass particles are not evenly distributed in the lifting tube because biomass clumps during conveying. Pneumatic conveying test setup and measurement system were built in this paper in order to study the agglomeration behavior of elongated biomass particles in the lifting tube experimentally. Particle tracking velocimetry (PTV) was used to determine the area distribution and velocity distribution of particles at different apparent air velocities and mass flow rates. The results show that while keeping the mass flow rate constant at 46.50 g/s, the apparent gas velocity increased from 5.91 to 7.91 m/s and the maximum size of agglomerates decreased from 0.689 to 0.235. The apparent gas velocity was kept at 6.40 m/s, and the particle mass flow rate was adjusted from 56.50 to 16.20 g/s. The maximum size of the agglomerates was reduced to 0.115. Therefore, appropriately increasing the apparent gas velocity or decreasing the particle mass flow rate can improve the uniformity of the particle distribution in the lifting tube. The results would provide a reference for parameter adjustment of pneumatic conveying devices in industrial production.

5.
ACS Appl Mater Interfaces ; 16(5): 6504-6512, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38267401

RESUMEN

Passive all-day radiative cooling (PARC) films with porous structures prepared via nonsolvent-induced phase separation (NIPS) have attracted considerable attention owing to their cost-effectiveness and wide applicability. The PARC performances of the films correlate with their porous structures. However, the porous structure formed using the NIPS process cannot be finely regulated. In this study, we prepared polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) films with porous structures optimized by rationally tuning the phase separation, which was achieved by adjusting the proportions of two good solvents with varying solubility parameters. The optimized PVDF-HFP film with a hierarchically porous structure exhibited a high solar reflectance of 97.7% and an infrared emissivity of 96.7%. The film with excellent durability achieved an average subambient cooling temperature of approximately 5.4 °C under a solar irradiance of 945 W·m-2 as well as a temperature of 11.2 °C at nighttime, thus demonstrating all-day radiative cooling. The results indicate that the proposed films present a promising platform for large-scale applications in green building cooling and achieving carbon neutrality.

6.
J Neuroradiol ; 51(2): 155-167, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37844660

RESUMEN

Cerebral small vessel disease (CSVD) is characterized by widespread functional changes in the brain, as evident from abnormal brain activations during cognitive tasks. However, the existing findings in this area are not yet conclusive. We systematically reviewed 25 studies reporting task-related fMRI in five cognitive domains in CSVD, namely executive function, working memory, processing speed, motor, and affective processing. The findings highlighted: (1) CSVD affects cognitive processes in a domain-specific manner; (2) Compensatory and regulatory effects were observed simultaneously in CSVD, which may reflect the interplay between the negative impact of brain lesion and the positive impact of cognitive reserve. Combined with behavioral and functional findings in CSVD, we proposed an integrated model to illustrate the relationship between altered activations and behavioral performance in different stages of CSVD: functional brain changes may precede and be more sensitive than behavioral impairments in the early pre-symptomatic stage; Meanwhile, compensatory and regulatory mechanisms often occur in the early stages of the disease, while dysfunction/decompensation and dysregulation often occur in the late stages. Overall, abnormal hyper-/hypo-activations are crucial for understanding the mechanisms of small vessel lesion-induced behavioral dysfunction, identifying potential neuromarker and developing interventions to mitigate the impact of CSVD on cognitive function.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Humanos , Imagen por Resonancia Magnética , Encéfalo/patología , Cognición , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología
7.
iScience ; 26(6): 106862, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37275516

RESUMEN

Liver cancer stem-like cells (LCSCs) are the main cause of heterogeneity and poor prognosis in hepatocellular carcinoma (HCC). In this study, we aimed to explore the origin of LCSCs and the role of the TOP2A/ß-catenin/YAP1 axis in tumor stemness and progression. Using single-cell RNA-seq analysis, we identified TOP2A+CENPF+ LCSCs, which were mainly regulated by CD168+ M2-like macrophages. Furthermore, spatial location analysis and fluorescent staining confirmed that LCSCs were enriched at tumor margins, constituting the spatial heterogeneity of HCC. Mechanistically, TOP2A competitively binds to ß-catenin, leading to disassociation of ß-catenin from YAP1, promoting HCC stemness and overgrowth. Our study provides valuable insights into the spatial transcriptome heterogeneity of the HCC microenvironment and the critical role of TOP2A/ß-catenin/YAP1 axis in HCC stemness and progression.

8.
Elife ; 122023 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-37216274

RESUMEN

Cells have evolved the DNA damage response (DDR) pathways in response to DNA replication stress or DNA damage. In the ATR-Chk1 DDR pathway, it has been proposed that ATR is recruited to RPA-coated single-stranded DNA (ssDNA) by direct ATRIP-RPA interaction. However, it remains elusive how ATRIP is recruited to ssDNA in an RPA-independent manner. Here, we provide evidence that APE1 directly associates ssDNA to recruit ATRIP onto ssDNA in an RPA-independent fashion. The N-terminal motif within APE1 is required and sufficient for the APE1-ATRIP interaction in vitro and the distinct APE1-ATRIP interaction is required for ATRIP recruitment to ssDNA and the ATR-Chk1 DDR pathway activation in Xenopus egg extracts. In addition, APE1 directly associates with RPA70 and RPA32 via two distinct motifs. Taken together, our evidence suggests that APE1 recruits ATRIP onto ssDNA in an RPA-dependent and -independent manner in the ATR DDR pathway.


Asunto(s)
ADN de Cadena Simple , Proteína de Replicación A , Fosforilación , Proteína de Replicación A/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Replicación del ADN , Daño del ADN , Proteínas de Ciclo Celular/metabolismo
9.
Addict Biol ; 28(6): e13284, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37252878

RESUMEN

Proactive inhibition is a critical ability for smokers who seek to moderate or quit smoking. It allows them to pre-emptively refrain from seeking and using nicotine products, especially when facing salient smoking cues in daily life. Nevertheless, there is limited knowledge on the impact of salient cues on behavioural and neural aspects of proactive inhibition, especially in smokers with nicotine withdrawal. Here, we seek to bridge this gap. To this end, we recruited 26 smokers to complete a stop-signal anticipant task (SSAT) in two separate sessions: once in the neutral cue condition and once in the smoking cue condition. We used graph-based modularity analysis to identify the modular structures of proactive inhibition-related network during the SSAT and further investigated how the interactions within and between these modules could be modulated by different proactive inhibition demands and salient smoking cues. Findings pointed to three stable brain modules involved in the dynamical processes of proactive inhibition: the sensorimotor network (SMN), cognitive control network (CCN) and default-mode network (DMN). With the increase in demands, functional connectivity increased within the SMN, CCN and between SMN-CCN and decreased within the DMN and between SMN-DMN and CCN-DMN. Salient smoking cues disturbed the effective dynamic interactions of brain modules. The profiles for those functional interactions successfully predicted the behavioural performance of proactive inhibition in abstinent smokers. These findings advance our understanding of the neural mechanisms of proactive inhibition from a large-scale network perspective. They can shed light on developing specific interventions for abstinent smokers.


Asunto(s)
Señales (Psicología) , Nicotina , Humanos , Fumadores , Inhibición Proactiva , Imagen por Resonancia Magnética , Encéfalo , Fumar/psicología , Mapeo Encefálico
10.
Medicine (Baltimore) ; 102(7): e33004, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36800576

RESUMEN

Overexpression of SCL/TAL1 interrupting locus (STIL) has been observed in various cancer types. However, the clinical significance of STIL in hepatocellular carcinoma (HCC) remains unknown. Cox regression and Kaplan-Meier survival analyses were performed to evaluate the prognostic value of STIL. Go and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were also carried out. Immune infiltrates analyses were conducted based on TIMER (Tumor Immune Estimation Resource) and GAPIA databases. STIL expression was highly expressed in HCC tissues, based on multiple databases. KEGG and GO enrichment analysis showed STIL-related to tumorigenesis and progress. Furthermore, STIL was significantly correlated with immune infiltration. STIL serves as a biomarker for the prediction of patient survival.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinogénesis , Transformación Celular Neoplásica , Relevancia Clínica , Pronóstico , Péptidos y Proteínas de Señalización Intracelular
11.
Nanoscale Adv ; 5(3): 711-724, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36756511

RESUMEN

Nano-filler reinforced polymer-based composites have attracted extensive attention in tribology; however, to date, it is still challenging to construct a favorable lubricating system with excellent compatibility, lubricity and durability using nano-filler reinforced polymer-based composites. Herein, sulfonated boron nitride nano-sheets (h-BN@PSDA) are prepared and used as nano-fillers for epoxy resins (EPs), to improve friction and wear along with thermal conductivity. Furthermore, inspired by the lubricating principle and structure of snail mucus, a solvent-free carbon dot-based nanofluid (F-CDs) is fabricated and used for the first time as the lubricant for h-BN@PSDA/EPs. Both poly (4-styrene sulfonate) and polyether amine grafted on the surface of F-CDs contribute to branched structures and multiple interfacial absorption effects. Extraordinarily low friction and wear are detected after long-term sliding. The average coefficient of friction and wear rate of h-BN@PSDA/EPs composites are reduced by 95.25% and 99.42% respectively, in the presence of the F-CD nanofluid, compared to that of EPs. Besides, the added h-BN nano-sheets increase the thermal conductivity (TC) of EPs from 0.178 to 0.194 W (m-1 K-1). The distinguished lubrication performances are likely due to the formation of a hybrid nanostructure of 0D F-CDs and 2D h-BN@PSDA together with the "rolling-sliding" and "self-mending" effects of added F-CDs.

12.
Nanomaterials (Basel) ; 13(1)2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36616112

RESUMEN

The excessively leached metal ions from traditional metallic antimicrobial nanoparticles are harmful to biological and human tissues. Metal-organic frameworks (MOFs) coordinating bioactive metal ions to organic bridging ligands can potentially address this issue, avoiding the excessive leaching of metal ions and simultaneously exhibiting high effective antibacterial activities. Here, we report the preparation of a 2-dimensional leaves-like zeolitic imidazolate framework (ZIF-L) for potential antibacterial and anti-algae applications. The ZIF-L nanosheet exhibits complete inactivation of Escherichia coli (phosphate buffer saline: 4 h) and Bacillus subtilis (seawater: 0.5 h). The ZIF-L/epoxy composite has excellent antibacterial effect, poisoning effect and anti-adhesion effect on a variety of marine algae. It is worth noting that the removal rate (Escherichia coli) for ZIF/epoxy composite can be reached to 90.20% by only adding ZIF-L (0.25 wt%). This work will inspire researchers to develop more metal-organic frameworks materials for applications in the antibacterial and anti-algae fields.

13.
Cereb Cortex ; 33(5): 1739-1751, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-35511695

RESUMEN

Recent neurocognitive models propose that the insula serves as a hub of interoceptive awareness system, modulating 2 interplaying neurocognitive systems: The posterior insula (PI) receives and integrates various interoceptive signals; these signals are then transmitted to the anterior insula for processing higher-order representations into awareness, where the dorsal anterior insula (dAI) modulates the prefrontal self-control system and the ventral anterior insula (vAI) modulates the amygdala (AMG)-striatal reward-seeking circuit. We sought to test this view using a multimodal approach. We first used a resting-state functional magnetic resonance imaging (fMRI) approach with a sample of 120 undergraduate students. Then, we unpacked the neuro-cognitive association between insular connectivity and cognitive performance during an Iowa gambling fMRI task. Lastly, an independent Open Southwest University Longitudinal Imaging Multimodal dataset was used to validate the results. Findings suggested that the dAI was predominantly connected to the prefrontal regions; the vAI was primarily connected to the AMG-ventral-striatum system; and the PI was mainly connected to the visceral-sensorimotor system. Moreover, cognitive scores were positively correlated with FC between dAI and the self-control process of ventrolateral prefrontal cortex and were negatively correlated with FC between vAI and the reward-seeking process of orbitofrontal cortex and subgenual anterior cingulate cortex. The findings highlight the roles of our theorized subinsular functionality in the overall operation of the neural cognitive systems.


Asunto(s)
Corteza Cerebral , Sustancia Blanca , Humanos , Giro del Cíngulo , Imagen por Resonancia Magnética , Corteza Insular , Mapeo Encefálico/métodos
14.
Cereb Cortex ; 33(8): 4688-4698, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-36178117

RESUMEN

The nondemented old-old over the age of 80 comprise a rapidly increasing population group; they can be regarded as exemplars of successful aging. However, our current understanding of successful aging in advanced age and its neural underpinnings is limited. In this study, we measured the microstructural and network-based topological properties of brain white matter using diffusion-weighted imaging scans of 419 community-dwelling nondemented older participants. The participants were further divided into 230 young-old (between 72 and 79, mean = 76.25 ± 2.00) and 219 old-old (between 80 and 92, mean = 83.98 ± 2.97). Results showed that white matter connectivity in microstructure and brain networks significantly declined with increased age and that the declined rates were faster in the old-old compared with young-old. Mediation models indicated that cognitive decline was in part through the age effect on the white matter connectivity in the old-old but not in the young-old. Machine learning predictive models further supported the crucial role of declines in white matter connectivity as a neural substrate of cognitive aging in the nondemented older population. Our findings shed new light on white matter connectivity in the nondemented aging brains and may contribute to uncovering the neural substrates of successful brain aging.


Asunto(s)
Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Envejecimiento/psicología , Imagen de Difusión por Resonancia Magnética , Mapeo Encefálico
15.
RSC Adv ; 12(49): 31699-31710, 2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36380949

RESUMEN

Hydrosilylation epoxidized eugenol (HSI-EP-EU) is successfully synthesized and used as a reactive diluent for epoxy/anhydride (marked as P) and epoxy/imidazole (marked as I) curing systems. The reactive bio-based diluent HSI-EP-EU has an excellent dilution effect on petroleum-based epoxy resin (E44). The curing kinetics of P + HSI-EP-EU and I + HSI-EP-EU are studied by a non-isothermal DSC method. The kinetics parameters are calculated by using the Kissinger model, Crnae model, Ozawa model and ß-T (temperature-heating speed) extrapolation, respectively, to determine theoretically reasonable curing conditions. In addition, the effects of HSI-EP-EU on the antibacterial properties, thermo-mechanical properties and thermal stability of P + HSI-EP-EU and I + HSI-EP-EU systems are also studied. It is found that HSI-EP-EU possessed obvious antibacterial properties and could effectively improve the mechanical properties for the I + HSI-EP-EU.

16.
Front Genet ; 13: 996890, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36303541

RESUMEN

Tumors are a class of diseases characterized by altered genetic information and uncontrolled growth. Sequencing technology provide researchers with a better way to explore specific tumor pathogenesis. In recent years, single-cell sequencing technology has shone in tumor research, especially in the study of liver cancer, revealing phenomena that were unexplored by previous studies. Single-cell sequencing (SCS) is a technique for sequencing the cellular genome, transcriptome, epigenome, proteomics, or metabolomics after dissociation of tissues into single cells. Compared with traditional bulk sequencing, single-cell sequencing can dissect human tumors at single-cell resolution, finely delineate different cell types, and reveal the heterogeneity of tumor cells. In view of the diverse pathological types and complex pathogenesis of hepatocellular carcinoma (HCC), the study of the heterogeneity among tumor cells can help improve its clinical diagnosis, treatment and prognostic judgment. On this basis, SCS has revolutionized our understanding of tumor heterogeneity, tumor immune microenvironment, and clonal evolution of tumor cells. This review summarizes the basic process and development of single-cell sequencing technology and its increasing role in the field of hepatocellular carcinoma.

17.
Front Genet ; 13: 1001195, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36299597

RESUMEN

Stalk lodging, or breakage of the stalk at or below the ear, is one of the vital factors causing substantial yield losses in maize (Zea mays. L). Lodging affects maize plants' physiological and molecular processes, eventually impacting plant growth and productivity. Despite this known fact, few researchers have investigated the genetic architecture underlying lodging in maize. Herein, through integrated transcriptome, metabolome, and phenotypic analyses of stalks of three diverse hybrid cultivars (highly resistant JNK738, mildly resistant JNK728, and lowly resistant XY335) at the tasseling (10 days to silking, 10 DTS) stage, we identified key genes and metabolic pathways modulating lodging resistance in maize. Based on the RNA-Seq analysis, a total of 10093 differentially expressed genes (DEGs) were identified from the comparison of the three varieties in pairs. Additionally, key lodging resistance-related metabolic pathways were obtained by KEGG enrichment analysis, and the DEGs were found predominantly enriched in phenylpropanoid and secondary metabolites biosynthesis pathways in the L_vs._H and M_vs._H comparison groups. Moreover, K-means analysis clustered the DEGs into clear and distinct expression profiles for each cultivar, with several functional and regulatory genes involved in the cell wall assembly, lignin biosynthetic process and hormone metabolic process being identified in the special clusters related to lodging resistance. Subsequently, integrating metabolome and transcriptome analyses revealed nine key lignin-associated metabolites that showed different expression trends in the three hybrid cultivars, among which L-phenylalanine and p-coumaric acid were regarded as differentially changed metabolites (DCMs). These two DCMs belonged to phenylalanine metabolism and biosynthesis pathways and were also supported by the RNA-Seq data. Furthermore, plant hormone signal transduction pathway-related genes encoding auxin, abscisic acid, jasmonates, and salicylic acid were differentially expressed in the three comparisons of lodging resistance, indicating these DEGs were valuable potential targets for improving maize lodging resistance. Finally, comparative physiological and qRT-PCR analyses results supported our transcriptome-based findings. Our research not only provides a preliminary theoretical basis and experimental ideas for an in-depth study of the regulatory networks involved in maize lodging resistance regulation but also opens up new avenues for molecular maize stalk lodging resistance breeding.

18.
Oxid Med Cell Longev ; 2022: 4277254, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36299605

RESUMEN

DNA topoisomerases (TOPs) are dysregulated in various types of cancer. However, how TOP II-alpha (TOP2A) contributes to hepatocellular carcinoma (HCC) progression remains elusive. Cohort analysis revealed that the increased expression of TOP2A was associated with poor clinical outcomes and TOP2A was significantly upregulated in HCC tissues and cell lines. In vitro, TOP2A expression level is related to cell invasion and migration, which may be due to the alteration of epithelial-mesenchymal transition by the TOP2A. Moreover, we used verteporfin (a Hippo inhibitor) to test how the Hippo pathway promotes the effect of TOP2A on the HCC phenotype and found that TOP2A induces tumor progression through the Hippo pathway. Finally, miR-22-5p inhibited tumor progression by sponging TOP2A.


Asunto(s)
Carcinoma Hepatocelular , ADN-Topoisomerasas de Tipo II , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , ADN-Topoisomerasas de Tipo II/genética , ADN-Topoisomerasas de Tipo II/metabolismo , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Vía de Señalización Hippo/genética , Vía de Señalización Hippo/fisiología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , Verteporfina
19.
Nucleic Acids Res ; 50(18): 10503-10525, 2022 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-36200829

RESUMEN

Multifunctional protein APE1/APEX1/HAP1/Ref-1 (designated as APE1) plays important roles in nuclease-mediated DNA repair and redox regulation in transcription. However, it is unclear how APE1 regulates the DNA damage response (DDR) pathways. Here we show that siRNA-mediated APE1-knockdown or APE1 inhibitor treatment attenuates the ATR-Chk1 DDR under stress conditions in multiple immortalized cell lines. Congruently, APE1 overexpression (APE1-OE) activates the ATR DDR under unperturbed conditions, which is independent of APE1 nuclease and redox functions. Structural and functional analysis reveals a direct requirement of the extreme N-terminal motif within APE1 in the assembly of distinct biomolecular condensates in vitro and DNA/RNA-independent activation of the ATR DDR. Overexpressed APE1 co-localizes with nucleolar NPM1 and assembles biomolecular condensates in nucleoli in cancer but not non-malignant cells, which recruits ATR and activator molecules TopBP1 and ETAA1. APE1 protein can directly activate ATR to phosphorylate its substrate Chk1 in in vitro kinase assays. W119R mutant of APE1 is deficient in nucleolar condensation, and is incapable of activating nucleolar ATR DDR in cells and ATR kinase in vitro. APE1-OE-induced nucleolar ATR DDR activation leads to compromised ribosomal RNA transcription and reduced cell viability. Taken together, we propose distinct mechanisms by which APE1 regulates ATR DDR pathways.


Asunto(s)
Proteínas de Unión al ADN , Proteínas Nucleares , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Condensados Biomoleculares , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/genética , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/metabolismo , ADN , Daño del ADN , Proteínas de Unión al ADN/genética , Proteínas Nucleares/metabolismo , ARN Ribosómico/genética , ARN Interferente Pequeño/genética
20.
ACS Nano ; 16(10): 16724-16735, 2022 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-36215403

RESUMEN

Addressing the conflict between achieving high mechanical properties and room-temperature self-healing ability is extremely significant to achieving a breakthrough in the application of self-healing materials. Therefore, inspired by natural spider silk and nacre, a room-temperature self-healing supramolecular material with ultrahigh strength and toughness is developed by synergistically incorporating flexible disulfide bonds and dynamic sextuple hydrogen bonds (H-bonds) into polyurethanes (PUs). Simultaneously, abundant H-bonds are introduced at the interface between graphene oxide nanosheets with dynamic multiple H-bonds and the PU matrix to afford strong interfacial interactions. The resulting urea-containing PU material with an inverse artificial nacre structure has a record mechanical strength (78.3 MPa) and toughness (505.7 MJ m-3), superior tensile properties (1273.2% elongation at break), and rapid room-temperature self-healing abilities (88.6% at 25 °C for 24 h), forming the strongest room-temperature self-healing elastomer reported to date and thus upending the previous understanding of traditional self-healing materials. In addition, this bionic PU-graphene oxide network endows the fabricated flexible intelligent robot with functional repair and shape memory capabilities, thus providing prospects for the fabrication of flexible functional devices.


Asunto(s)
Nácar , Nácar/química , Poliuretanos/química , Temperatura , Elastómeros , Disulfuros , Seda , Urea
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...