Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 235
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Cell ; 166(4): 841-854, 2016 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-27453471

RESUMEN

For placental mammals, the transition from the in utero maternal environment to postnatal life requires the activation of thermogenesis to maintain their core temperature. This is primarily accomplished by induction of uncoupling protein 1 (UCP1) in brown and beige adipocytes, the principal sites for uncoupled respiration. Despite its importance, how placental mammals license their thermogenic adipocytes to participate in postnatal uncoupled respiration is not known. Here, we provide evidence that the "alarmin" IL-33, a nuclear cytokine that activates type 2 immune responses, licenses brown and beige adipocytes for uncoupled respiration. We find that, in absence of IL-33 or ST2, beige and brown adipocytes develop normally but fail to express an appropriately spliced form of Ucp1 mRNA, resulting in absence of UCP1 protein and impairment in uncoupled respiration and thermoregulation. Together, these data suggest that IL-33 and ST2 function as a developmental switch to license thermogenesis during the perinatal period. PAPERCLIP.


Asunto(s)
Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Parto , Termogénesis , Adipocitos/metabolismo , Animales , Animales Recién Nacidos , Respiración de la Célula , Frío , Femenino , Interleucina-33/genética , Linfocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL
2.
Cell ; 160(1-2): 74-87, 2015 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-25543153

RESUMEN

Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2- and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4Rα in PDGFRα(+) APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis. PAPERCLIP:


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Linfocitos/metabolismo , Adipocitos/citología , Adipocitos/metabolismo , Animales , Proliferación Celular , Femenino , Interleucina-13/metabolismo , Interleucina-33 , Interleucinas/inmunología , Linfocitos/citología , Masculino , Ratones , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptores de Interleucina-4/metabolismo , Transducción de Señal , Células Madre/metabolismo
4.
Stroke ; 55(3): 625-633, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38328909

RESUMEN

BACKGROUND: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. METHODS: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. RESULTS: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. CONCLUSIONS: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Anciano , Femenino , Humanos , Masculino , Administración Oral , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Estudios Multicéntricos como Asunto , Sistema de Registros
5.
J Intern Med ; 2024 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-39370680

RESUMEN

BACKGROUND: Limited evidence exists on the role of depression in the risk of developing stroke and other cardiovascular outcomes in patients who have undergone percutaneous coronary interventions (PCI). We investigated this relationship with data from the Korean National Health Insurance Service database. METHODS: Our nationwide retrospective cohort study included 164,198 patients who had undergone PCI between 2010 and 2017. Depression was defined with the ICD-10 codes recorded prior to the PCI. The primary outcome was a new-onset stroke following the PCI. Secondary outcomes included PCI with myocardial infarction (MI), revascularization (PCI or coronary artery bypass grafting), and all-cause mortality. A multivariable Cox proportional hazards regression analysis was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI), adjusting for potential confounders, including sociodemographic and lifestyle factors, comorbidities, and MI at the index PCI. RESULTS: Over a median follow-up of 5.0 years, acute stroke occurred in 5.7% of patients with pre-existing depression (17.4% of the study population), compared to 3.5% of those without depression. Depression was associated with a 27% increased risk of acute stroke (aHR 1.27, 95% CI 1.20-1.35). Additionally, depression was linked with a 25% elevated risk of all-cause death (aHR 1.25, 95% CI, 1.21-1.29) and an 8% increased risk of revascularization (aHR 1.08, 95% CI 1.04-1.11). The associations with the risk of stroke and all-cause mortality were stronger in patients under 65 years. CONCLUSIONS: Our findings suggest that pre-existing depression may increase the risk of stroke and all-cause mortality following PCI, particularly in patients under 65 years. Additionally, depression was significantly associated with an increased need for revascularization. This underscores the potential benefits of managing depression to reduce stroke risk and overall cardiovascular outcomes following PCI.

6.
Small ; 20(34): e2310943, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38607261

RESUMEN

The development of data-intensive computing methods imposes a significant load on the hardware, requiring progress toward a memory-centric paradigm. Within this context, ternary content-addressable memory (TCAM) can become an essential platform for high-speed in-memory matching applications of large data vectors. Compared to traditional static random-access memory (SRAM) designs, TCAM technology using non-volatile resistive memories (RRAMs) in two-transistor-two-resistor (2T2R) configurations presents a cost-efficient alternative. However, the limited sensing margin between the match and mismatch states in RRAM structures hinders the potential of using memory-based TCAMs for large-scale architectures. Therefore, this study proposes a practical device engineering method to improve the switching response of conductive-bridge memories (CBRAMs) integrated with existing complementary metal-oxide-semiconductor (CMOS) transistor technology. Importantly, this work demonstrates a significant improvement in memory window reaching 1.87 × 107 by incorporating nanocavity arrays and modifying electrode geometry. Consequently, TCAM cells using nanocavity-enhanced CBRAM devices can exhibit a considerable increase in resistance ratio up to 6.17 × 105, thereby closely approximating the sensing metrics observed in SRAM-based TCAMs. The improved sensing capability facilitates the parallel querying of extensive data sets. TCAM array simulations using experimentally verified device models indicate a substantial sensing margin of 65× enabling a parallel search of 2048 bits.

7.
Neuroepidemiology ; : 1-9, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38952140

RESUMEN

BACKGROUND: Smoking is a well-known risk factor for cardiovascular diseases, including myocardial infarction (MI) and ischemic stroke (IS). While the relationship between smoking and the risk of cardiovascular diseases is established, the impact of changing smoking habits post-IS on the risk of subsequent MI remains unclear. This study aims to elucidate the effects of alterations in smoking behavior following an IS diagnosis on the likelihood of experiencing an MI. METHODS: Utilizing data from the Korean National Health Insurance Services Database, this nationwide population-based cohort study included 199,051 participants diagnosed with IS between January 2010 and December 2016. Smoking status was categorized based on changes in smoking habits before and after IS diagnosis. The association between changes in smoking behavior and the risk of subsequent MI was analyzed using multivariable Cox proportional hazard regression models. RESULTS: During a median follow-up of 4.17 person-years, a total of 5,734 (2.88%) patients were diagnosed with MI after IS. Smoking quitters (2.93%) or former smokers (2.47%) have a similar or lower rate of MI than the average, even if they have smoked cigarettes, while sustained smokers (3.46%) or new smokers (3.81%) have much higher rates of MI. Among sustained and new smokers, the risk of incident MI was significantly higher than never smokers (new smoker adjusted HR [aHR]: 1.496, 95% CI: 1.262-1.774; sustained smoker aHR: 1.494, 95% CI: 1.361-1.641). Also, among the study participants, approximately two-thirds continued smoking after their IS diagnosis. CONCLUSION: Changing smoking habits after an IS diagnosis significantly influences the risk of subsequent MI. Specifically, continuing or starting to smoke after an IS diagnosis is associated with a higher risk of MI. These results underscore the importance of targeted smoking cessation interventions for stroke patients to reduce the risk of subsequent MI.

8.
Nanotechnology ; 35(29)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38608317

RESUMEN

Achieving energy-efficient and high-performance field-effect transistors (FETs) is one of the most important goals for future electronic devices. This paper reports semiconducting single-walled carbon nanotube FETs (s-SWNT-FETs) with an optimized high-krelaxor ferroelectric insulator P(VDF-TrFE-CFE) thickness for low-voltage operation. The s-SWNT-FETs with an optimized thickness (∼800 nm) of the high-kinsulator exhibited the highest average mobility of 14.4 cm2V-1s-1at the drain voltage (ID) of 1 V, with a high current on/off ratio (Ion/off>105). The optimized device performance resulted from the suppressed gate leakage current (IG) and a sufficiently large capacitance (>50 nF cm-2) of the insulating layer. Despite the extremely high capacitance (>100 nF cm-2) of the insulating layer, an insufficient thickness (<450 nm) induces a highIG, leading to reducedIDand mobility of s-SWNT-FETs. Conversely, an overly thick insulator (>1200 nm) cannot introduce sufficient capacitance, resulting in limited device performance. The large capacitance and sufficient breakdown voltage of the insulating layer with an appropriate thickness significantly improved p-type performance. However, a reduced n-type performance was observed owing to the increased electron trap density caused by fluorine proportional to the insulator thickness. Hence, precise control of the insulator thickness is crucial for achieving low-voltage operation with enhanced s-SWNT-FET performance.

9.
Retina ; 44(8): 1298-1304, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-39047124

RESUMEN

PURPOSE: To identify the extent of damage to the superficial vascular complex and deep vascular complex as the stage of diabetic retinopathy (DR) increases. METHODS: Subjects were divided into four groups: patients with type 2 diabetes without DR (Group 1), those with mild-to-moderate nonproliferative DR (Group 2), those with severe-to-very severe nonproliferative DR (Group 3), and those with proliferative DR (Group 4). The vessel densities of the superficial vascular complex (superficial vessel density, SVD) and deep vascular complex (deep vessel density, DVD) and their ratios were compared. Linear regression analyses were used to identify factors associated with the SVD/DVD ratio. RESULTS: The SVDs were 25.5% ± 6.1%, 25.1% ± 7.0%, 24.5% ± 9.0%, and 21.6% ± 6.9% (P = 0.048); the DVDs 25.6% ± 5.3%, 23.0% ± 7.0%, 22.3% ± 8.8%, and 17.5% ± 5.0% (P < 0.001); and the SVD/DVD ratios 1.00 ± 0.16, 1.12 ± 0.20, 1.14 ± 0.33, and 1.24 ± 0.27 (P < 0.001) in Groups 1 to 4, respectively. In multivariate analysis, DR severity (B = 7.16, P < 0.001) and the HbA1c level (B = 1.57, P = 0.042) were significantly associated with the SVD/DVD ratio. CONCLUSION: Both the SVD and DVD tended to decrease in the advanced stages of DR, and the SVD/DVD ratio increased, indicating more severe damage to the deep vascular complex than the superficial vascular complex. The ratio was positively associated with the HbA1c level, indicating a significant relationship between that level and DVD rather than SVD damage.


Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Angiografía con Fluoresceína , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Retinopatía Diabética/diagnóstico , Masculino , Femenino , Vasos Retinianos/patología , Vasos Retinianos/diagnóstico por imagen , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Anciano , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Agudeza Visual
10.
BMC Public Health ; 24(1): 1241, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711032

RESUMEN

BACKGROUND: The impact of changes in physical activity after ischemic stroke (IS) on the subsequent myocardial infarction (MI) risk is not fully understood. We aimed to investigate the effects of changes in physical activity on the risk of MI after acute IS using data from the Korean National Health Insurance Services Database. METHODS: 224,764 patients newly diagnosed with IS between 2010 and 2016 who underwent two serial biannual health checkups were included. The participants were divided into four categories according to changes in their physical activity: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was a new diagnosis of incident MI. Multivariable Cox proportional models were used to assess the effects of changes in exercise habits on the risk of MI. RESULTS: After a median of 4.25 years of follow-up, 6,611 (2.94%) MI cases were observed. After adjusting for confounders, new exercisers and exercise maintainers were significantly associated with a lower risk of incident MI than persistent non-exercisers (aHR, 0.849; 95% CI, 0.792-0.911; P-value < 0.001; and aHR, 0.746; 95% CI, 0.696-0.801; P-value < 0.001, respectively). Effects were consistent across sexes, more pronounced in those > 65 years. Notably, any level of physical activity after stroke was associated with a reduced MI risk compared to no exercise. CONCLUSIONS: In this nationwide cohort study, commencing or sustaining physical activity after an IS corresponded to a diminished likelihood of subsequent MI development. Advocating physical activity in ambulatory stroke survivors could potentially attenuate the prospective risk of MI.


Asunto(s)
Ejercicio Físico , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Humanos , Masculino , Femenino , Infarto del Miocardio/epidemiología , República de Corea/epidemiología , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/epidemiología , Anciano , Incidencia , Adulto , Factores de Riesgo
11.
Psychiatry Clin Neurosci ; 78(4): 229-236, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38113307

RESUMEN

AIM: Recovery from stroke is adversely affected by neuropsychiatric complications, cognitive impairment, and functional disability. Better knowledge of their mutual relationships is required to inform effective interventions. Network theory enables the conceptualization of symptoms and impairments as dynamic and mutually interacting systems. We aimed to identify interactions of poststroke complications using network analysis in diverse stroke samples. METHODS: Data from 2185 patients were sourced from member studies of STROKOG (Stroke and Cognition Consortium), an international collaboration of stroke studies. Networks were generated for each cohort, whereby nodes represented neuropsychiatric symptoms, cognitive deficits, and disabilities on activities of daily living. Edges characterized associations between them. Centrality measures were used to identify hub items. RESULTS: Across cohorts, a single network of interrelated poststroke complications emerged. Networks exhibited dissociable depression, apathy, fatigue, cognitive impairment, and functional disability modules. Worry was the most central symptom across cohorts, irrespective of the depression scale used. Items relating to activities of daily living were also highly central nodes. Follow-up analysis in two studies revealed that individuals who worried had more densely connected networks than those free of worry (CASPER [Cognition and Affect after Stroke: Prospective Evaluation of Risks] study: S = 9.72, P = 0.038; SSS [Sydney Stroke Study]: S = 13.56, P = 0.069). CONCLUSION: Neuropsychiatric symptoms are highly interconnected with cognitive deficits and functional disabilities resulting from stroke. Given their central position and high level of connectedness, worry and activities of daily living have the potential to drive multimorbidity and mutual reinforcement between domains of poststroke complications. Targeting these factors early after stroke may have benefits that extend to other complications, leading to better stroke outcomes.


Asunto(s)
Trastornos del Conocimiento , Disfunción Cognitiva , Accidente Cerebrovascular , Humanos , Depresión/psicología , Actividades Cotidianas/psicología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Trastornos del Conocimiento/complicaciones , Disfunción Cognitiva/complicaciones , Cognición
12.
J Korean Med Sci ; 39(34): e278, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39228188

RESUMEN

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.


Asunto(s)
Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Sistema de Registros , Humanos , República de Corea/epidemiología , Femenino , Ataque Isquémico Transitorio/epidemiología , Accidente Cerebrovascular Isquémico/epidemiología , Masculino , Anciano , Factores de Riesgo , COVID-19/epidemiología , Fibrilación Atrial/epidemiología , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Persona de Mediana Edad , Anticoagulantes/uso terapéutico , Incidencia , Accidente Cerebrovascular/epidemiología , Anciano de 80 o más Años , SARS-CoV-2 , Hipertensión/epidemiología , Hipertensión/complicaciones , Prevalencia
13.
Chaos ; 34(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39141794

RESUMEN

We derive and numerically validate a low-order oscillator model to capture the stochastic dynamics of a prototypical thermoacoustic system (a Rijke tube) undergoing a subcritical Hopf bifurcation in the presence of additive noise. We find that on the fixed-point branch before the bifurcation, the system is dominated by the first duct mode, and the Fokker-Planck solution for the first Galerkin mode can adequately predict the stochastic dynamics of the overall system. We also find that this analytical framework predicts well the dominant mode on the limit-cycle branch, but underperforms in the hysteretic bistable zone where the role of nonlinearities is more pronounced. Besides offering new insights into stochastic thermoacoustic behavior, this study shows that an analytical framework based on the Fokker-Planck equation can facilitate the early detection of thermoacoustic instabilities in a Rijke-tube model subjected to noise.

14.
Sensors (Basel) ; 24(14)2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39066136

RESUMEN

The delivery market in Republic of Korea has experienced significant growth, leading to a surge in motorcycle-related accidents. However, there is a lack of comprehensive data collection systems for motorcycle safety management. This study focused on designing and implementing a foundational data collection system to monitor and evaluate motorcycle driving behavior. To achieve this, eleven risky behaviors were defined, identified using image-based, GIS-based, and inertial-sensor-based methods. A motorcycle-mounted sensing device was installed to assess driving, with drivers reviewing their patterns through an app and all data monitored via a web interface. The system was applied and tested using a testbed. This study is significant as it successfully conducted foundational data collection for motorcycle safety management and designed and implemented a system for monitoring and evaluation.

15.
Clin Gerontol ; 47(5): 832-845, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38372125

RESUMEN

OBJECTIVES: The goal of this study was to develop and evaluate an intervention aimed at increasing cognitive empathy, improving mental health, and reducing inflammation in dementia caregivers, and to examine the relevant neural and psychological mechanisms. METHODS: Twenty dementia caregivers completed an intervention that involved taking 3-5 daily photographs of their person living with dementia (PLWD) over a period of 10 days and captioning those photos with descriptive text capturing the inner voice of the PLWD. Both before and after the intervention, participants completed questionnaires, provided a blood sample for measures of inflammation, and completed a neuroimaging session to measure their neural response to viewing photographs of their PLWD and others. RESULTS: 87% of enrolled caregivers completed the intervention. Caregivers experienced pre- to post-intervention increases in cognitive empathy (i.e. Perspective-Taking) and decreases in both burden and anxiety. These changes were paralleled by an increased neural response to photographs of their PLWD within brain regions implicated in cognitive empathy. CONCLUSION: These findings warrant a larger replication study that includes a control condition and follows participants to establish the duration of the intervention effects. CLINICAL IMPLICATIONS: Cognitive empathy interventions may improve caregiver mental health and are worthy of further investigation.


Asunto(s)
Cuidadores , Demencia , Empatía , Fotograbar , Humanos , Cuidadores/psicología , Empatía/fisiología , Femenino , Demencia/psicología , Masculino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Ansiedad/psicología , Encuestas y Cuestionarios , Cognición/fisiología , Terapia Cognitivo-Conductual/métodos , Salud Mental
16.
J Cell Physiol ; 238(10): 2335-2347, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37659097

RESUMEN

Matrix stiffness has been shown to play a critical role in cancer progression by influencing various cellular processes, including epidermal growth factor (EGF) signaling. However, the underlying molecular mechanisms are not fully understood. Here, we investigated the role of adaptor-related protein complex 1 subunit sigma 1 (AP1S1), a component of adaptor protein complex-1, in the regulation of EGF receptor (EGFR) intracellular trafficking during cancer cell progression. We found that AP1S1 expression was upregulated under stiff matrix conditions, resulting in the regulation of EGFR trafficking in non-small cell lung adenocarcinoma cells. Knockout of AP1S1 caused the lysosomal degradation of EGFR, leading to suppressed EGF-induced anaplastic lymphoma receptor tyrosine kinase phosphorylation. In addition, the downregulation of AP1S1 increased the sensitivity of H1975 cancer cells, which are resistant to tyrosine kinase inhibitors, to erlotinib. Collectively, our results suggest that AP1S1 could regulate EGFR recycling under stiff matrix conditions, and AP1S1 inhibition could be a novel strategy for treating cancer cells resistant to EGFR-targeted anticancer drugs.

17.
J Am Chem Soc ; 145(41): 22620-22632, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37799086

RESUMEN

Nanostructured silicon with an equilibrium shape has exhibited hydrogen evolution reaction activity mainly owing to its high surface area, which is distinct from that of bulk silicon. Such a Wulff shape of silicon favors low-surface-energy planes, resulting in silicon being an anisotropic and predictably faceted solid in which certain planes are favored, but this limits further improvement of the catalytic activity. Here, we introduce nanoporous silicon nanosheets that possess high-surface-energy crystal planes, leading to an unconventional Wulff shape that bolsters the catalytic activity. The high-index plane, uncommonly seen in the Wulff shape of bulk Si, has a band structure optimally aligned with the redox potential necessary for hydrogen generation, resulting in an apparent quantum yield (AQY) of 12.1% at a 400 nm wavelength. The enhanced light absorption in nanoporous silicon nanosheets also contributes to the high photocatalytic activity. Collectively, the strategy of making crystals with nontypical Wulff shapes can provide a route toward various classes of photocatalysts for hydrogen production.

18.
Cerebrovasc Dis ; 52(4): 427-434, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36273453

RESUMEN

INTRODUCTION: Cerebral small vessel disease (SVD) burden includes increased risk of poor functional outcomes after acute ischemic stroke (AIS). We aimed to investigate the impact of cerebral SVD on 3-month functional outcomes in patients with AIS who received endovascular treatment (EVT) and to determine whether SVD is associated with futile reperfusion (FR). METHODS: Using a multicenter stroke registry, we analyzed consecutive patients with AIS with either intracranial and/or extracranial anterior circulation large artery occlusion, who were treated with EVT and achieved successful reperfusion (thrombolysis in cerebral infarction grade 2b-3). The cerebral SVD burden was evaluated using baseline brain magnetic resonance imaging using a modified Fazekas score (mFS). The main outcome variable was FR, defined as poor functional outcomes (modified Rankin scale 3-6) at 3 months after stroke, despite successful recanalization. Secondary outcomes included stroke progression/recurrence and any hemorrhagic transformation. RESULTS: Among 10,890 patients with AIS, 577 (5.3%) received EVT within 12 h of onset, including 354 who met study eligibility criteria. FR was observed in 191 patients (53.5%) and was positively associated with SVD burden. After adjustment for covariates including age, sex, stroke etiology, initial stroke severity, collateral status, Alberta stroke program early CT score, initial serum glucose, systemic blood pressure, and vascular risk factors, mFS grade 3 was significantly associated with FR (odds ratio: 3.93, 95% confidence interval: 1.602-9.619; p = 0.003). CONCLUSIONS: We demonstrated that cerebral SVD assessed with baseline brain MRI is associated with the futility of successful recanalization after EVT and any hemorrhagic transformation but not with early stroke progression or recurrence. Nevertheless, our findings do not justify withholding EVT in otherwise eligible patients with AIS based on the presence of severe SVD.


Asunto(s)
Isquemia Encefálica , Enfermedades de los Pequeños Vasos Cerebrales , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/etiología , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia , Isquemia Encefálica/patología , Inutilidad Médica , Resultado del Tratamiento , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/patología , Reperfusión/efectos adversos , Reperfusión/métodos
19.
Cerebrovasc Dis ; 52(1): 44-51, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35537405

RESUMEN

INTRODUCTION: Glycated hemoglobin is widely used for the diagnosis of diabetes, but it is not accurately correlated with blood glucose fluctuations. We evaluated the impact of prestroke glycemic variability, measured by glycated albumin (GA) on reperfusion rate and stroke outcomes after endovascular treatment (EVT). METHODS: We consecutively collected 310 EVT-treated patients for 60 months using a multicenter registry database. Primary outcome was unsuccessful reperfusion defined by modified Thrombolysis in Cerebral Infarction grade 0 to 2a. Secondary outcomes were occurrence of early neurologic deterioration (END), symptomatic hemorrhagic transformation (SHT) and a 3-month poor outcome (modified Rankin Scale >2). GA was measured in the morning after hospital admission with overnight fasting and determined to reflect high prestroke glycemic variability (GA ≥16.0%). RESULTS: Over the median follow-up of 60 months of 310 patients, there were 64 (20.6%) events of unsuccessful reperfusion, 66 (21.3%) of END, 21 (6.8%) of SHT, and 180 (58.1%) of 3-month poor outcome. In the higher GA group (130, 41.9%), proportion of unsuccessful reperfusion, END, SHT, and poor outcome were higher than lower GA group. The multivariate analysis showed that higher GA was associated with unsuccessful reperfusion after EVT (adjusted odds ratio 4.13; 95% confidence interval [CI], 1.93-8.85). The area under the receiver operating characteristic of GA (0.644; 95% CI: 0.634-0.740) for predicting poor outcome was better than that of glycated hemoglobin (0.586; 95% CI: 0.529-0.642, p for DeLong's pairwise comparison = 0.005). CONCLUSION: GA, reflecting prestroke glycemic variability, could be a reliable parameter for predicting reperfusion rate and acute ischemic stroke outcome in this study.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Resultado del Tratamiento , Hemoglobina Glucada , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/etiología , Pronóstico , Albúmina Sérica , Procedimientos Endovasculares/efectos adversos , Isquemia Encefálica/terapia
20.
BMC Neurol ; 23(1): 106, 2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36918775

RESUMEN

OBJECTIVES: We evaluated the impact of malnutrition as estimated by the controlling nutritional status (CONUT) score and prognostic nutritional index (PNI) on hemorrhagic transformation (HT) and stroke outcomes after intravenous thrombolysis (IVT). MATERIALS AND METHODS: Using a multicenter registry database, we enrolled 808 patients with acute ischemic stroke who received IVT between August 2013 and May 2021. We defined malnutrition as a CONUT score ≥ 2 and low PNI. The primary outcome measure was the occurrence of symptomatic HT contributing to early neurologic deterioration (END-SHT) after IVT. Multivariable analysis was performed to analyze the association between CONUT score, PNI, and END-SHT after IVT. RESULTS: The rate of END-SHT was higher with increasing CONUT scores and PNI values. In the multivariable analysis, CONUT score ≥ 5 and low PNI were significantly associated with END-SHT (odds ratio [95% confidence interval], CONUT score ≥ 5: 12.23 [2.41-62.07], p = 0.003; low PNI: 4.98 [1.76-14.09], p = 0.003). The receiver operating characteristic curve showed that both the CONUT score and PNI had good predictive ability. The cutoff values for CONUT and PNI were 5 and 42.3, respectively, for END-SHT. CONCLUSION: Malnutrition, as denoted by a higher CONUT score and lower PNI, was associated with END-SHT. The joint application of both nutritional markers could be useful in predicting END-SHT after IVT.


Asunto(s)
Accidente Cerebrovascular Isquémico , Desnutrición , Accidente Cerebrovascular , Humanos , Pronóstico , Estudios Retrospectivos , Desnutrición/complicaciones , Desnutrición/epidemiología , Estado Nutricional , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Terapia Trombolítica
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA