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Optoelectronic synapses are currently drawing significant attention as fundamental building blocks of neuromorphic computing to mimic brain functions. In this study, a two-terminal synaptic device based on a doped PdSe2 flake is proposed to imitate the key neural functions in an optical pathway. Due to the wavelength-dependent desorption of oxygen clusters near the intrinsic selenide vacancy defects, the doped PdSe2 photodetector achieves a high negative photoresponsivity of -7.8 × 103 A W-1 at 473 nm and a positive photoresponsivity of 181 A W-1 at 1064 nm. This wavelength-selective bi-direction photoresponse endows an all-optical pathway to imitate the fundamental functions of artificial synapses on a device level, such as psychological learning and forgetting capability, as well as dynamic logic functions. The underpinning photoresponse is further demonstrated on a flexible platform, providing a viable technology for neuromorphic computing in wearable electronics. Furthermore, the p-type doping results in an effective increase of the channel's electrical conductivity and a significant reduction in power consumption. Such low-power-consuming optical synapses with simple device architecture and low-dimensional features demonstrate tremendous promise for building multifunctional artificial neuromorphic systems in the future.
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BACKGROUND AND PURPOSE: Caveolin-1 (Cav-1) is reported to mediate blood-brain barrier integrity after ischaemic stroke. Our purpose was to assess the role of circulating Cav-1 levels in predicting symptomatic intracranial haemorrhage (sICH) amongst ischaemic stroke patients after endovascular thrombectomy (EVT). METHODS: Patients with large-vessel occlusive stroke after EVT from two stroke centres were prospectively included. Serum Cav-1 level was tested after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of 325 patients (mean age 68.6 years; 207 men) included, 47 (14.5%) were diagnosed with sICH. Compared with patients without sICH, those with sICH had a lower concentration of Cav-1. After adjusting for potential confounders, multivariate regression analysis demonstrated that the increased Cav-1 level was associated with a lower sICH risk (odds ratio 0.055; 95% confidence interval 0.005-0.669; p = 0.038). Similar results were obtained when Cav-1 levels were analysed as a categorical variable. Using a logistic regression model with restricted cubic splines, a linear and negative association of Cav-1 concentration was found with sICH risk (p = 0.001 for linearity). Furthermore, the performance of the conventional risk factors model in predicting sICH was substantially improved after addition of the Cav-1 levels (integrated discrimination index 2.7%, p = 0.002; net reclassification improvement 39.7%, p = 0.007). CONCLUSIONS: Our data demonstrate that decreased Cav-1 levels are related to sICH after EVT. Incorporation of Cav-1 into clinical decision-making may help to identify patients at a high risk of sICH and warrants further consideration.
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Caveolina 1 , Procedimentos Endovasculares , Hemorragias Intracranianas , AVC Isquêmico , Trombectomia , Idoso , Feminino , Humanos , Masculino , Caveolina 1/sangue , Procedimentos Endovasculares/efeitos adversos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/epidemiologia , AVC Isquêmico/sangue , AVC Isquêmico/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: Atherogenic index of plasma (AIP) is a newly identified as marker of lipid metabolism and glucose metabolism, showing significant predictive value in individuals with cardiovascular disease. This study aimed to explore the correlation between AIP and early neurological deterioration (END) in ischemic stroke patients after mechanical thrombectomy (MT). METHODS: Patients with anterior circulation large artery occlusive stroke who underwent MT were retrospectively enrolled from 2 stroke center in China. The AIP is a logarithmically transformed ratio of triglycerides to high-density lipoprotein cholesterol. END was defined as an increase of ≥ 4 point in National Institutes of Health Stroke Scale within 24 hours after surgery. Multivariable regression analysis and restricted cubic spline was utilized to determine the association of AIP index with risk of END. RESULTS: Of 601 patients (mean age, 70.2 ± 12.1 years; 62.1% of male) enrolled, 91 (15.1%) experienced postoperative END. After adjustment for potential confounders, higher AIP levels were significantly associated with an increased risk of END after MT treatment (Per 1-standard deviation increase; odd ratio, 1.474; 95% confidence interval, 1.162-1.869, P=0.001). Similar results were confirmed when the AIP was analyzed as a categorical variable. Restricted cubic spline further demonstrated a linear relationship between AIP and risk of END (P=0.001 for linearity). CONCLUSIONS: The present study found that a higher AIP index were associated with END in acute ischemic stroke patients following MT treatment for emergent large vessel occlusion.
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BACKGROUND AND PURPOSE: The Chinese Visceral Adiposity Index (CVAI) is a reliable indicator of visceral adiposity dysfunction in the Chinese population. We aimed to evaluate the association between CVAI and clinical outcome in Chinese ischemic stroke patients who received endovascular thrombectomy (EVT). METHODS: This study retrospectively included patients with large vessel occlusive stroke receiving EVT treatment in 2 China stroke centers. Baseline CVAI was calculated after admission. Patients with a modified Rankin scale score ≥ 3 at 3 months after ischemic stroke were defined as poor outcome. Binary multivariate logistic regression models were utilized to explore the association between CVAI and the risk of 90-day unfavorable outcome. RESULTS: A total of 453 patients (mean age, 70.4 ± 12.1 years; 280 male) were included. During the 90-day follow-up, 236 (52.1 %) patients experienced poor outcome. After multivariable adjustment for potential confounders, increasing CVAI was associated with an increased risk of 90-day poor outcome (odds ratios, per-standard deviation increase: 1.521; 95 % confidence interval, 1.127-2.052; P = 0.006). Similar significant results were observed when the CVAI was analyzed as a categorical variable. Furthermore, the multiple-adjusted spline regression model showed an inverted J-shape association between CVAI and risk of unfavorable outcome (P = 0.048 for non-linearity). CONCLUSIONS: This study demonstrated that CVAI is positively correlated with 90-day poor outcome in Chinese ischemic stroke patients after EVT.
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Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Adiposidade , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , AVC Isquêmico/etiologia , Trombectomia/efeitos adversos , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversosRESUMO
Hypoxia affects fish's survival, growth, and physiological metabolism processes. In this study, turbot plasma glucose and cortisol contents, hepatic glycolysis (hexokinase [HK], phosphofructokinase [PFK], pyruvate kinase [PK]) and lipolysis (fatty acid synthetase [FAS], lipoprotein lipase [LPL]) enzyme activities, anti-oxidant enzyme (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]) activities, malondialdehyde (MDA), lactate and glycogen contents, gill histological parameters (lamellar length [SLL], width [SLW], interlamellar distance [ID]), respiratory frequency (RF), the proportion of the secondary lamellae available for gas exchange (PAGE), and hifs (hif-1α, hif-2α, hif-3α) expression were determined during long-term hypoxia and reoxygenation. Results showed that long-term hypoxia (3.34 ± 0.17 mg L-1) significantly elevated plasma cortisol and glucose contents; increased hepatic HK, PK, PFK, FAS, and LPL activity; decreased hepatic glycogen, lactate contents, and lipid drop numbers; and caused changes of hepatocyte (vacuolation, pyknotic, and lytic nucleus) after treatment for 4 weeks. Hepatic SOD, CAT, GSH-Px activity, and MDA contents; lamellar perimeter, SLL, ID, RF, and PAGE; and hepatic hif-1α, hif-2α, and hif-3α manifested similar results. Meanwhile, hif-1α is significantly higher than hif-2α, and hif-3α. Interestingly, females and males demonstrated no sex dimorphism significantly different from the above parameters (except hepatic FAS, LPL activity, and lipid drop number) under hypoxia. The above parameters recovered to normal levels after reoxygenation treatment for 4 weeks. Thus, long-term hypoxia promotes turbot hepatic glycogenolysis and lipolysis, induces oxidative damage and stimulates hepatic antioxidant capacity, and alters gill morphology to satisfy insufficient energy demand and alleviate potential damage, while hif-1α plays critical roles in the above physiological process.
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BACKGROUND: Studies have shown that people with internet gaming disorder (IGD) exhibit impaired executive control of gaming cravings; however, the neural mechanisms underlying this process remain unknown. In addition, these conclusions were based on the hypothesis that brain networks are temporally static, neglecting dynamic changes in cognitive processes. METHODS: Resting-state fMRI data were collected from 402 subjects [162 subjects with IGD and 240 recreational game users (RGUs)]. The community structure (recruitment and integration) of the executive control network (ECN) and the basal ganglia network (BGN), which represents the reward network, of patients with IGD and RGUs were compared. Mediation effects among the different networks were analyzed. RESULTS: Compared to RGUs, subjects with IGD had a lower recruitment coefficient within the right ECN. Further analysis showed that only male subjects had a lower recruitment coefficient. Mediation analysis showed that the integration coefficient of the right ECN mediated the relationship between the recruitment coefficients of both the right ECN and the BGN in RGUs. CONCLUSIONS: Male subjects with IGD had a lower recruitment coefficient than RGUs, which impairing their impulse control. The mediation results suggest that top-down executive control of the ECN is absent in subjects with IGD. Together, these findings could explain why subjects with IGD exhibit impaired executive control of gaming cravings; these results have important therapeutic implications for developing effective interventions for IGD.
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Mapeamento Encefálico , Transtorno de Adição à Internet , Humanos , Masculino , Mapeamento Encefálico/métodos , Transtorno de Adição à Internet/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Recompensa , Internet , Função ExecutivaRESUMO
INTRODUCTION: Endothelial dysfunction (ED) may result in parenchymal injury and therefore worsen the outcomes of ischemic stroke. This study aimed to determine whether ED could predict parenchymal hematoma (PH) in ischemic stroke patients treated with endovascular thrombectomy (EVT). METHODS: Patients with large artery occlusion in the anterior circulation and treated with EVT were prospectively enrolled from 2 stroke centers. Serum soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-selectin, and von Willebrand factor (vWF) were tested and summed to a standardized score to reflect the levels of ED. PH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of the 325 enrolled patients (mean age, 68.6 years; 207 men), 41 (12.6%) developed PH. Patients with PH had higher concentrations of soluble E-selectin, vWF, and ED sum score. After adjusting for demographic characteristics, National Institutes of Health Stroke Scale score, pretreatment Alberta stroke program early computed tomography score, and other potential confounders, the increased ED burden was associated with PH (odds ratio, 1.432; 95% confidence interval, 1.031-1.988; p = 0.032). Similar significant results were found in the sensitivity analysis. The multiple-adjusted spline regression model showed a linear association between the total ED score and PH (p = 0.001 for linearity). Adding the ED score to the conventional model significantly improved the risk prediction of PH (net reclassification improvement = 25.2%, p = 0.001; integrated discrimination index = 2.9%; p = 0.001). CONCLUSIONS: This study demonstrated that ED might be related to PH. Introducing the ED score could increase the reliability of the PH risk model for stroke patients treated with EVT.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Idoso , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/terapia , Selectina E , Reprodutibilidade dos Testes , Fator de von Willebrand , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Trombectomia/métodos , Hematoma/etiologia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: The impact of serum caveolin-1 (Cav-1) on clinical outcomes in patients after mechanical thrombectomy (MT) is unclear. We aimed to investigate the association between serum cav-1 levels and the 3-month functional outcome. METHODS: We prospectively enrolled and analyzed patients with an anterior circulation large vessel occlusion who underwent MT. Serum cav-1 concentrations were tested after admission. The primary outcome was a 90-day modified Rankin Scale score of 3-6. RESULTS: Of the 237 recruited patients (mean age, 69.7 ± 12.1 years; 152 male), 131 (55.3%) experienced a 90-day poor outcome. After adjustment for demographic characteristics and other covariates, patients with higher serum Cav-1 levels had a reduced risk of poor outcome at 3 months (Per 1-standard deviation increase; odd ratios [OR], 0.59; 95% confidence interval [CI], 0.39 - 0.89, P = 0.013). Elevated Cav-1 concentrations (Per 1-standard deviation increase; OR, 0.59; 95% CI, 0.40 - 0.88, P = 0.011) were significantly associated with a favorable shift in modified Rankin Scale score distribution. Similar results were confirmed when the Cav-1 levels were analyzed as a categorical variable. Furthermore, the restricted cubic spline showed a linear association between Cav-1 levels and 90-day poor outcome (P = 0.032 for linearity). CONCLUSIONS: Increased serum Cav-1 levels were associated with improved prognosis at 3 months in ischemic stroke patients after MT, suggesting that Cav-1 may be a potential prognostic biomarker for ischemic stroke after reperfusion therapy.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Encefálica/cirurgia , Caveolina 1 , AVC Isquêmico/etiologia , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/cirurgia , Trombectomia , Resultado do TratamentoRESUMO
Food cravings can reflect an intense trait-like emotional-motivational desire to eat palatable food, often resulting in the failure of weight loss efforts. Studies have linked trait-based food-cravings to increased risk of overeating. However, little is known about resting-state neural mechanisms that underlie food cravings. We investigated this issue using resting-state functional magnetic resonance imaging (fMRI) to test the extent to which spontaneous neural activity occurs in regions implicated in emotional memory and reward motivation associated with food cravings. Spontaneous regional activity patterns correlating to food cravings were assessed among 65 young healthy women using regional homogeneity analysis to assess temporal synchronization of spontaneous activity. Analyses indicated that women with higher scores on the Food Cravings Questionnaire displayed increased local functional homogeneity in brain regions involved in emotional memory and visual attention processing (i.e., parahippocampal gyrus and fusiform gyrus) but not reward. In view of parahippocampal gyrus involvement in hedonic learning and incentive memory encoding, this study suggests that trait-based food cravings are encoded by emotional memory circuits.
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Fissura/fisiologia , Comportamento Alimentar/fisiologia , Giro Para-Hipocampal/fisiologia , Adolescente , Adulto , Mapeamento Encefálico/métodos , Emoções/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Motivação/fisiologia , Estudantes , Adulto JovemRESUMO
Theory and associated research indicate that people with elevated restrained eating (RE) scores have higher risk for binge eating, future bulimic symptom onset and weight gain. Previous imaging studies have suggested hyper-responsive reward brain area activation in response to food cues contributes to this risk but little is known about associated neural impulse control mechanisms, especially when considering links between depleted cognitive resources related to unsuccessful RE. Towards illuminating this issue, we used a chocolate-specific delayed discounting (DD) task to investigate relations between RE scores, behavior impulsivity, and corresponding neural impulse control correlates in a functional magnetic resonance imaging (fMRI) study of 27 young women. Specifically, participants were required to choose between more immediate, smaller versus delayed, larger hypothetical chocolate rewards following initial consumption of a chocolate. As predicted, RE scores were correlated positively with behavior impulse control levels. More critically, higher RE scores were associated with stronger activation in impulse control region, the dorsal-lateral prefrontal cortex (DLPFC) during the completion of difficult decision trials reflecting higher cognitive demands and resource depletion relative to easy decision trials. Exploratory analyses revealed a positive correlation between RE scores and activity in a reward system hub, the right striatum. Moreover, a positive correlation between left DLPFC and striatum activation was posited to reflect, in part, impulse control region compensation in response to stronger reward signal among women with RE elevations. Findings suggested impulse control lapses may contribute to difficulties in maintaining RE, particularly when cognitive demands are high.
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Restrição Calórica/psicologia , Chocolate , Desvalorização pelo Atraso , Ingestão de Alimentos/psicologia , Comportamento Impulsivo , Índice de Massa Corporal , Encéfalo/fisiologia , Comportamento de Escolha , Cognição , Sinais (Psicologia) , Feminino , Preferências Alimentares/psicologia , Comportamentos Relacionados com a Saúde , Humanos , Imageamento por Ressonância Magnética , Avaliação Nutricional , Projetos Piloto , Inquéritos e Questionários , Aumento de Peso , Adulto JovemRESUMO
Background: Liver fibrosis has been reported to be associated with hematoma expansion and mortality in patients with intracerebral hemorrhage. This study aimed to detect the association between liver fibrosis and symptomatic intracranial hemorrhage (sICH) in ischemic stroke after mechanical thrombectomy (MT). Methods: We retrospectively included patients with large artery occlusion in the anterior circulation and treated with MT at a single stroke center. The fibrosis-4 index (FIB-4) was used to assess the severity of liver fibrosis. sICH was diagnosed according to the Heidelberg Bleeding Classification criteria. Multivariate logistic regression and restricted cubic spline analysis were conducted to examine the relationship between liver fibrosis and sICH. Results: Among the 578 patients (mean age, 70.1 years; 58.5% male) included in the study, 65 (11.2%) individuals were diagnosed with sICH. After adjusting for demographic characteristics and other potential confounders, a higher FIB-4 index was found to be independently associated with an increased risk of sICH (odds ratio: 1.306, 95% confidence interval: 1.127-1.512, P=0.001). Similar results were obtained when analyzing FIB-4 as a categorical variable. Conclusion: This study demonstrated that there is a significant association between FIB-4 and the risk of sICH in patients with acute ischemic stroke who underwent MT. Therefore, liver fibrosis could serve as a valuable parameter in monitoring the risk of sICH following MT.
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Oxidative stress induced endothelial dysfunction plays a particularly important role in promoting the development of cardiovascular diseases (CVDs). Salvianolic acid A (SalA) is a water-soluble component of traditional Chinese medicine Salvia miltiorrhiza Bunge with anti-oxidant potency. This study aims to explore the regulatory effect of SalA on oxidative injury using an in vitro model of H2O2-induced injury in human umbilical vein endothelial cells (HUVECs). In the study, we determined cell viability, the activities of Lactate dehydrogenase (LDH) and Superoxide dismutase (SOD), cell proliferation rate and intracellular reactive oxygen species (ROS). Flow cytometry was used to detect cell apoptosis. Western-blotting was used to evaluate the expression of cell senescence, apoptosis, autophagy and pyroptosis protein factors. The expression level of miRNA was determined by qRT-PCR. Compared with H2O2-induced HUVECs, SalA promoted cell viability and cell proliferation rate; decreased LDH and ROS levels; and increased SOD activity. SalA also significantly attenuated endothelial senescence, inhibited cell apoptosis, reversed the increase of LC3 II/I ratio and NLRP3 accumulation. Furthermore, miR-204-5p was regulated by SalA. Importantly, miR-204-5p inhibitor had similar effect to that of SalA on H2O2-induced HUVECs. Our results indicated that SalA could alleviate H2O2-induced oxidative injury by downregulating miR-204-5p in HUVECs.
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Apoptose , Sobrevivência Celular , Células Endoteliais da Veia Umbilical Humana , Peróxido de Hidrogênio , Lactatos , MicroRNAs , Estresse Oxidativo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Peróxido de Hidrogênio/toxicidade , Peróxido de Hidrogênio/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Lactatos/farmacologia , Lactatos/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Autofagia/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Antioxidantes/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genéticaRESUMO
Waste activated sludge serves an important reservoir for antibiotics within wastewater treatment plants, and understanding the occurrence and evolution of antibiotics during sludge treatment is crucial to mitigate the potential risks of subsequent resource utilization of sludge. This study explores the degradation and transformation mechanisms of three typical antibiotics, oxytetracycline (OTC), ofloxacin (OFL), and azithromycin (AZI) during sludge hydrothermal treatment (HT), and investigates the influence of biopolymers transformation on the fate of these antibiotics. The findings indicate that HT induces a shift of antibiotics from solid-phase adsorption to liquid-phase dissolution in the initial temperature range of 25-90 °C, underscoring this phase's critical role in preparing antibiotics for subsequent degradation phases. Proteins (PN) and humic acids emerge as crucial for antibiotic binding, facilitating their redistribution within sludge. Specifically, the binding capacity sequence of biopolymers to antibiotics is as follows: OFL>OTC>AZI, highlighting that OFL-biopolymers display stronger electrostatic attraction, more available adsorption sites, and more stable binding strength. Furthermore, antibiotic degradation mainly occurs above 90 °C, with AZI being the most temperature-sensitive, degrading 92.97% at 180 °C, followed by OTC (91.26%) and OFL (52.51%). Concurrently, the degradation products of biopolymers compete for active sites to form novel amino acid-antibiotic conjugates, which inhibits the further degradation of antibiotics. These findings illuminate the effects of biopolymers evolution on intricate dynamics of antibiotics fate in sludge HT and are helpful to optimize the sludge HT process for effective antibiotics abatement.
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Antibacterianos , Esgotos , Esgotos/química , Antibacterianos/química , Biopolímeros/química , Adsorção , Poluentes Químicos da Água/química , Eliminação de Resíduos Líquidos , Azitromicina/química , TemperaturaRESUMO
BACKGROUND: Neuroscientific evidence suggests that the pathological symptoms associated with autism spectrum disorders (ASD) are not confined to a single brain region but involve networks of the brain on a larger spatial scale. Analyzing diagrams of edge-edge interactions could provide important perspectives on the organization and function of complex systems. METHODS: Resting-state fMRI data from 238 ASD patients and 311 healthy controls (HCs) were included in the current study. We used the thalamus as the mediating node to calculate the edge functional connectivity (eFC) of the brain network and compared the ASD subjects and HCs. RESULTS: Compared with the HCs, the ASD subjects exhibited abnormalities in the central node thalamus and four brain regions (amygdala, nucleus accumbens, pallidum and hippocampus), as well as in the eFC formed by the inferior frontal gyrus (IFG) (or middle temporal gyrus (MTG)). In addition, ASD subjects showed variable characteristics of the eFC between nodes in different networks. CONCLUSIONS: The changes in these brain regions may be due to the disturbance in the reward system, which leads to coherence in the instantaneous comovement of the functional connections formed by these brain regions in ASD. This notion also reveals a functional network feature between the cortical and subcortical regions in ASD.
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Transtorno do Espectro Autista , Humanos , Transtorno do Espectro Autista/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION: Neutrophil extracellular traps play a role in the pathophysiology of stroke and are associated with severity and mortality. We aimed to investigate whether the citrullinated histone H3 (CitH3), a biomarker for neutrophil extracellular traps formation, is associated with the white matter lesion (WML) burden in ischemic stroke patients. METHODS: Between September 2021 and April 2022, 322 patients were enrolled in this prospective observational cohort study. Serum CitH3 levels were measured after admission using an enzyme-linked immunosorbent assay. WMLs severity was graded according to the Fazekas scale and conceptually defined as mild (total Fazekas score 0-2) and severe (total Fazekas score 3-6). We used multivariable regression models to determine the relationship between CitH3 concentrations and the severity of WMLs burden. RESULTS: One-hundred and forty-eight (46.0%) patients were diagnosed with severe WMLs burden after admission. Increased CitH3 levels (first quartile vs. fourth quartile of H3Cit, odds ratio, 3.311, 95% confidence interval, 1.336-8.027; p = 0.011) were independently associated with a greater WML burden in the fully adjusted multivariable model. Similar results were found when the H3Cit was analyzed as a continuous variable. Furthermore, the multiple-adjusted spline regression model showed a linear association between H3Cit levels and severe WMLs (P = 0.001 for linearity). CONCLUSIONS: In the present study, increased CitH3 levels were positively associated with extensive WMLs in ischemic stroke patients, indicating a role of neutrophil extracellular traps formation in the pathogenesis of WMLs.
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Background and Purpose: Little is known about the effect of soluble adhesion molecules on malignant brain edema (MBE) after endovascular thrombectomy (EVT). This study aimed to explore the association between serum concentrations of E-selectin and the risk of MBE in patients who received EVT. Methods: Patients with a large vessel occlusion stroke in the anterior circulation who underwent EVT were prospectively recruited. Serum soluble E-selectin concentrations were measured after admission for all patients. MBE was defined as a midline shift of ≥5 mm on follow-up imaging within 72 h after surgery. Multivariate logistic regression analyses were performed to determine the association between E-selectin levels and the risk of MBE. Results: Among the 261 included patients (mean age, 69.7 ± 12.3 years; 166 males), 59 (22.6%) developed MBE. Increasing circulating E-selectin levels were associated with an increased risk of MBE after multivariable adjustment (odds ratios [OR], highest vs. lowest quartile: 3.593; 95% confidence interval [CI], 1.178-10.956; p = 0.025). We further observed a significantly positive association between E-selectin and MBE (per 1-standard deviation increase; OR, 1.988; 95% CI, 1.379-2.866, p = 0.001) when the E-selectin levels were analyzed as a continuous variable. Furthermore, the restricted cubic spline demonstrated a linear correlation between serum E-selectin levels and the risk of MBE (p < 0.001 for linearity). Conclusions: In this prospective study, circulating levels of E-selectin were associated with an increased risk of MBE after EVT. Further mechanistic studies are warranted to elucidate the pathophysiology underlying this association.
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Background and Purpose: Insulin resistance plays a pivotal role in the pathophysiology of ischemic stroke. This study aimed to determine the relationship between the novel metabolic score for insulin resistance (METS-IR) and symptomatic intracranial hemorrhage (sICH) after endovascular thrombectomy (EVT) in stroke patients. Methods: We retrospectively included patients with large artery occlusion in the anterior circulation and treated by EVT from 2 stroke centers (Nanjing First Hospital from September 2019 to April 2022, and Jinling Hospital from September 2019 to July 2021). The METS-IR was used as an alternative marker of insulin resistance and calculated using laboratory data after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. Results: Of the 410 enrolled patients (mean age, 69.8 ± 11.7 years; 60.7% men), 50 (12.2%) were diagnosed as sICH. After adjusting for demographic characteristics, poor collateral status, and other potential confounders, higher METS-IR was revealed to be independently associated with sICH (odds ratio, 1.076; 95% confidence interval, 1.034-1.120; P = 0.001). Similar significant results were obtained when defining METS-IR as a categorical variable. The restricted cubic spline uncovered a linear relationship between METS-IR and sICH (P < 0.001 for linearity). Furthermore, adding METS-IR to the conventional model significantly improved the risk prediction for sICH (net reclassification improvement = 15.8%, P = 0.035; integrated discrimination index = 2.6%; P = 0.017). Conclusion: This study demonstrated a significant association between METS-IR score and sICH in ischemic stroke patients treated with EVT. It could help monitor and manage sICH in patients after EVT.
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Purpose: Our previous study has shown that AVE 0991, a nonpeptide analogue of Ang-(1-7), ameliorates cognitive decline and inhibits NLRP3 inflammasome of astrocytes in Alzheimer's disease model mice. Additionally, several studies have suggested that activation of autophagy appears to effectively inhibit the progression of neuroinflammation. However, it is unclear whether AVE 0991 can modulate astrocyte autophagy to suppress neuroinflammation in Alzheimer's disease. Materials and Methods: APP/PS1 mice and Aß-treated primary astrocytes were used as the research objects in vivo and in vitro, respectively. Water maze test was used to evaluate cognitive function of mice, Nissl staining and immunofluorescence staining was used to assess neuronal damage. ELISA kits were used to detect the levels of Ang-(1-7) and Aß in the cortex, and qRT-PCR was used to detect the expression of cortical inflammation-related mediators. The expression of autophagy-related proteins in cortex were detected by Western blot. The upstream molecular responses involved in inflammation inhibition by AVE 0991 were validated by means of using the Mas1 antagonist and autophagy inhibitor. Results: We found that 30 days of intraperitoneal administration of AVE 0991 improved. Aß deposition, neuronal death, and cognitive deficits in APP/PS1 Alzheimer's disease model mice. Moreover, AVE 0991 treatment greatly suppressed astrocyte-mediated inflammation and up-regulated the expression of autophagy. Furthermore, the inhibitory effect of AVE 0991 on the expression of inflammatory factors was reversed by 3-MA, an autophagy inhibitor. Conclusion: These findings suggest that regulation of autophagy is critical for inhibiting astrocyte neuroinflammatory responses and demonstrate a potential neuroprotective mechanism by which AVE 0991 could suppress neuroinflammatory responses by enhancing autophagy.
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Previously, we reported that H157Y, a rare coding variant on exon 3 of the triggering receptor expressed on myeloid cells 2 gene (TREM2), was associated with Alzheimer's disease (AD) risk in a Han Chinese population. To date, how this variant increases AD risk has remained unclear. In this study, using CRISPR-Cas9-engineered BV2 microglia, we tried to investigate the influence of the Trem2 H157Y variant on AD-related microglial functions. For the first time, we revealed that the Trem2 H157Y variant inhibits microglial phagocytosis of amyloid-ß, promotes M1-type polarization of microglia, and facilitates microglial release of inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. These findings provide new insights into the cellular mechanisms by which the TREM2 H157Y variant elevates the risk of AD.
RESUMO
Triggering receptor expressed on myeloid cells-like 2 (TREML2) is a newly identified susceptibility gene for Alzheimer's disease (AD). It encodes a microglial inflammation-associated receptor. To date, the potential role of microglial TREML2 in neuroinflammation in the context of AD remains unclear. In this study, APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression. In addition, lipopolysaccharide (LPS) stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD. Our results show that TREML2 levels gradually increased in the brains of APP/PS1 mice during disease progression. LPS stimulation of primary microglia led to the release of inflammatory cytokines including interleukin-1ß, interleukin-6, and tumor necrosis factor-α in the culture medium. The LPS-induced microglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knockdown. LPS increased the levels of microglial M1-type polarization marker inducible nitric oxide synthase. This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown. Furthermore, the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown. LPS stimulation increased the levels of NLRP3 in primary microglia. The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown. In summary, this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation. These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.