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Utilizing a microfluidic chip with serpentine channels, we inoculated the chip with an agar plug with Neurospora crassa mycelium and successfully captured individual hyphae in channels. For the first time, we report the presence of an autonomous clock in hyphae. Fluorescence of a mCherry reporter gene driven by a clock-controlled gene-2 promoter (ccg-2p) was measured simultaneously along hyphae every half an hour for at least 6 days. We entrained single hyphae to light over a wide range of day lengths, including 6,12, 24, and 36 h days. Hyphae tracked in individual serpentine channels were highly synchronized (K = 0.60-0.78). Furthermore, hyphae also displayed temperature compensation properties, where the oscillation period was stable over a physiological range of temperatures from 24 °C to 30 °C (Q10 = 1.00-1.10). A Clock Tube Model developed could mimic hyphal growth observed in the serpentine chip and provides a mechanism for the stable banding patterns seen in race tubes at the macroscopic scale and synchronization through molecules riding the growth wave in the device.
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Hifa , Neurospora crassa , Neurospora crassa/genética , Neurospora crassa/fisiología , Neurospora crassa/crecimiento & desarrollo , Hifa/crecimiento & desarrollo , Hifa/genética , Temperatura , Dispositivos Laboratorio en un Chip , Regulación Fúngica de la Expresión Génica , Relojes Biológicos/genéticaRESUMEN
The presence of Arbuscular Mycorrhizal Fungi (AMF) in vascular land plant roots is one of the most ancient of symbioses supporting nitrogen and phosphorus exchange for photosynthetically derived carbon. Here we provide a multi-scale modeling approach to predict AMF colonization of a worldwide crop from a Recombinant Inbred Line (RIL) population derived from Sorghum bicolor and S. propinquum. The high-throughput phenotyping methods of fungal structures here rely on a Mask Region-based Convolutional Neural Network (Mask R-CNN) in computer vision for pixel-wise fungal structure segmentations and mixed linear models to explore the relations of AMF colonization, root niche, and fungal structure allocation. Models proposed capture over 95% of the variation in AMF colonization as a function of root niche and relative abundance of fungal structures in each plant. Arbuscule allocation is a significant predictor of AMF colonization among sibling plants. Arbuscules and extraradical hyphae implicated in nutrient exchange predict highest AMF colonization in the top root section. Our work demonstrates that deep learning can be used by the community for the high-throughput phenotyping of AMF in plant roots. Mixed linear modeling provides a framework for testing hypotheses about AMF colonization phenotypes as a function of root niche and fungal structure allocations.
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Micorrizas , Raíces de Plantas , Sorghum , Micorrizas/fisiología , Raíces de Plantas/microbiología , Sorghum/microbiología , Modelos Lineales , Simbiosis , Redes Neurales de la ComputaciónRESUMEN
The widespread use of silver nanoparticles (AgNPs) in commercial and industrial applications has led to their increased presence in the environment, raising concerns about their ecological and health impacts. This study pioneers an investigation into the chronic versus short-term acute toxicological impacts of differently coated AgNPs on zebrafish, with a novel focus on the thyroid-disrupting effects previously unexplored. The results showed that acute toxicity ranked from highest to lowest as AgNO3 (0.128 mg/L), PVP-AgNPs (1.294 mg/L), Citrate-AgNPs (6.984 mg/L), Uncoated-AgNPs (8.269 mg/L). For bioaccumulation, initial peaks were observed at 2 days, followed by fluctuations over time, with the eventual highest enrichment seen in Uncoated-AgNPs and Citrate-AgNPs at concentrations of 13 and 130 µg/L. Additionally, the four exposure groups showed a significant increase in T3 levels, which was 1.28-2.11 times higher than controls, and significant changes in thyroid peroxidase (TPO) and thyroglobulin (TG) content, indicating thyroid disruption. Gene expression analysis revealed distinct changes in the HPT axis-related genes, providing potential mechanisms underlying the thyroid toxicity induced by different AgNPs. The higher the Ag concentration in zebrafish, the stronger the thyroid disrupting effects, which in turn affected growth and development, in the order of Citrate-AgNPs, Uncoated-AgNPs > AgNO3, PVP-AgNPs. This research underscores the importance of considering nanoparticle coatings in risk assessments and offers insights into the mechanisms by which AgNPs affect aquatic organisms' endocrine systems, highlighting the need for careful nanotechnology use and the relevance of these findings for understanding environmental pollutants' role in thyroid disease.
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Nanopartículas del Metal , Plata , Glándula Tiroides , Contaminantes Químicos del Agua , Pez Cebra , Animales , Plata/toxicidad , Plata/química , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Contaminantes Químicos del Agua/toxicidad , Bioacumulación , Tiroglobulina/metabolismoRESUMEN
N6-Methyladenine (6mA) of DNA has emerged as a novel epigenetic mark in eukaryotes, and several 6mA effector proteins have been identified. However, efforts to selectively inhibit the biological functions of these effector proteins with small molecules are unsuccessful to date. Here we report the first potent and selective small molecule inhibitor (13h) of AlkB homologue 1 (ALKBH1), the only validated 6mA demethylase. 13h showed an IC50 of 0.026 ± 0.013 µM and 1.39 ± 0.13 µM in the fluorescence polarization (FP) and enzyme activity assay, respectively, and a KD of 0.112 ± 0.017 µM in the isothermal titration calorimetry (ITC) assay. The potency of 13h was well explained by the cocrystal structure of the 13h-ALKBH1 complex. Furthermore, 13h displayed excellent selectivity for ALKBH1. In cells, compound 13h and its derivative 16 were able to engage ALKBH1 and modulate the 6mA levels. Collectively, our study identified the first potent, isoform selective, and cell-active ALKBH1 inhibitor, providing a tool compound for exploring the biological functions of ALKBH1 and DNA 6mA.
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ADN , Eucariontes , ADN/metabolismo , Eucariontes/metabolismo , Metilación de ADNRESUMEN
Camel milk has unique compositional, functional and therapeutic properties compared to cow's milk and also contains many protective proteins with anti-cancer, anti-diabetic and anti-bacterial properties. In this experiment, fresh camel milk was heat-treated at different temperatures and times, and the changes in Millard reaction products were analyzed. Meanwhile, headspace-gas chromatography-ion migration spectrometry (HS-GC-IMS), electronic nose and electronic tongue were used to analyze the changes of volatile components in camel milk after different heat treatments. The results showed that the Maillard reaction was more severe with the increase of heat treatment, and the contents of furosine and 5-hydroxymethylfurfural increased significantly when the heat treatment temperature was higher than 120°C. HS-GC-IMS results showed that the contents of aldehydes and ketones increased obviously with the increase of heat treatment degree. The study clarifies the effects of different heat treatment degrees on Maillard reaction degree and flavor of camel milk, which has practical production guidance significance for the research and industrialization of liquid camel milk products.
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Background: Fibroblast growth factor 1 (FGF1) is extensively amplified in many tumors and accelerates tumor invasion and metastasis. However, the role and precise molecular mechanism by which FGF1 participates in thyroid cancer (TC) are still unclear. Methods: Quantitative real-time polymerase chain reaction- and western blotting were used to detect the mRNA and protein levels of FGF1, high mobility group A (HMGA1), epithelial-to-mesenchymal transition (EMT)-related factors, and FGFs in both TC tissues and cell lines. Immunohistochemistry was conducted to examine the expression of FGF1 and HMGA1. Immunofluorescence staining was used to detect the coexpression of FGF1 and HMGA1. Transwell and wound healing assays were conducted to evaluate the effects of FGF1 on the capacity of invasion and migration in cells. Results: FGF1 was upregulated in papillary thyroid carcinoma (PTC) tissues and cell lines and was relatively higher in PTC tissues with cervical lymph node metastasis. Furthermore, FGF1 promotes invasion and metastasis through the EMT pathway. Mechanistically, FGF1 promotes EMT through intracellular function independent of FGF receptors. Interestingly, we demonstrated that FGF1 could upregulate HMGA1 in TC cells, and the correlation of FGF1 and HMGA1 was positive in PTC tissues. FGF1 and HMGA1 had obvious colocalization in the nucleus. We further revealed that FGF1 promotes the invasion and migration of TC cells through the upregulation of HMGA1. Conclusion: Intracellular FGF1 could promote invasion and migration in TC by mediating the expression of HMGA1 independent of FGF receptors, and FGF1 may be an effective therapeutic target in TC.
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Due to the heterogeneity of amyloid ß-42 (Aß42) species, the potential correlation between plasma oligomeric Aß42 (oAß42) and cognitive impairments in cerebral small vessel disease (CSVD) remains unclear. Herein, a sandwich ELISA for the specific detection of Aß42 oligomers (oAß42) and total Aß42 (tAß42) was developed based on sequence- and conformation-specific antibody pairs for the evaluation of plasma samples from a Chinese CSVD community cohort. After age and gender matching, 3-Tesla magnetic resonance imaging and multidimensional cognitive assessment were conducted in 134 CSVD patients and equal controls. The results showed that plasma tAß42 and oAß42 levels were significantly elevated in CSVD patients. By regression analysis, these elevations were correlated with the presence of CSVD and its imaging markers (i.e., white matter hyperintensities). Plasma Aß42 tests further strengthened the predictive power of vascular risk factors for the presence of CSVD. Relative to tAß42, oAß42 showed a closer correlation with memory domains evaluated by neuropsychological tests. In conclusion, this sensitive ELISA protocol facilitated the detection of plasma Aß42; Aß42, especially its oligomeric form, can serve as a biosensor for the presence of CSVD and associated cognitive impairments represented by memory domains.
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Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Humanos , Péptidos beta-Amiloides , Fragmentos de Péptidos , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/patología , Enfermedades de los Pequeños Vasos Cerebrales/psicologíaRESUMEN
BACKGROUND: Cerebral atherosclerotic stenosis (CAS) is a significant factor in the development of acute ischemic stroke (AIS). Previous studies have reported that cytokines are involved in atherosclerotic diseases, although the relationship between serum levels of the chemokine RANTES (regulated on activation, normal T-cell expressed and secreted) and the presence of CAS remains unclear. METHODS: In total, 127 participants (65 non-AIS controls and 62 patients with AIS) were involved in this study. CAS was defined as the presence of ≥ 50% stenosis in major intracranial or extracranial artery by a Digital Substraction Angiography (DSA) examination, and we classified all participants into four groups according to stroke and CAS status. Serum concentrations of 8 cytokines, including RANTES, were measured by the Human ProcartaPlex Multiplex Immunoassay Kit. RESULTS: Seventy-eight participants (61.41%) had CAS, of which 39 cases with AIS and 39 case with non-AIS. Patients with CAS had higher RANTES levels compared to non-CAS patients in both the non-AIS group (10.54 ± 0.80 vs. 13.20 ± 0.71, p = 0.016) and stroke group (11.96 ± 0.87 vs. 15.03 ± 0.75, p = 0.011), and multivariate logistic regression analysis showed that the RANTES level is independently associated with CAS in both the non-AIS group (adjusted odds ratio (OR), 1.07; 95% CI, 1.02-1.12, P = 0.004) and stroke group (adjusted OR, 1.32; 95% CI, 1.10-1.58, P = 0.003). CONCLUSION: Patients with CAS have higher levels of serum RANTES than non-CAS patients regardless of stroke status suggesting that RANTES may play an important role in the formation of CAS.
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Estenosis Carotídea , Quimiocina CCL5 , Arteriosclerosis Intracraneal , Accidente Cerebrovascular Isquémico , Humanos , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Constricción Patológica , Citocinas , Arteriosclerosis Intracraneal/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Factores de Riesgo , Quimiocina CCL5/sangreRESUMEN
Background: Cerebral small vessel disease (SVD) is common in the aging population. The study aimed to evaluate the effect of SVD on functional outcomes in patients with acute ischemic stroke (AIS) receiving endovascular treatment (EVT). Methods: From a prospective registry, we selected patients with AIS receiving EVT. SVD features, including white matter hyperintensities (WMH), lacunes and brain atrophy, were assessed on MRI and a validated SVD score was calculated to reflect the total SVD burden. Results: Among 137 patients included, 106 had none-mild SVD burden and 31 had moderate-severe SVD burden. The moderate-severe SVD burden group showed a significantly higher modified Rankin Scale score at 90 d (median, 4 versus 1 points, adjusted common odds ratio 0.32 [95% CI, 0.14-0.69], P < 0.01) and a significantly smaller improvement of NIHSS at 24 h (median, -3 versus -3 points, adjusted ß coefficient 4.02 [95% CI, 0.57-7.48], P = 0.02) and 7 days (median, -4 versus -6 points, adjusted ß coefficient 4.71 [95% CI, 1.06-8.36], P = 0.01) than the none-mild group. There was no significant difference in successful recanalization, death within 90 days, symptomatic intracranial hemorrhage within 24 h between two groups (all P > 0.05). Additionally, for each single SVD feature, brain atrophy and WMH, but not lacunes, were associated with the functional outcome. Conclusion: Moderate-severe SVD burden was associated with poor early and late functional outcomes in patients with AIS receiving EVT. Our results suggest that SVD score may act as a good predictor of outcomes in these patients.
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AlkB homolog 5 (ALKBH5) is an RNA m6A demethylase involved in the regulation of genes transcription, translation and metabolism and has been considered as a promising therapeutic target for various human diseases, especially cancers. However, there is still a lack of potent and selective ALKBH5 inhibitors. Herein, we report a new class of ALKBH5 inhibitors containing the 1-aryl-1H-pyrazole scaffold, which were obtained through fluorescence polarization-based screening, structural optimization and structure-activity relationship analysis. Among these compounds, 20m was the most potent one, which showed an IC50 value of 0.021 µM in fluorescence polarization assay. Compound 20m exhibited high selectivity towards ALKBH5 versus FTO as well as other AlkB subfamily members, indicating good selectivity for ALKBH5. Cellular thermal shift assay (CETSA) analysis showed that 20m could efficiently stabilize ALKBH5 in HepG2 cells. Dot blot assay demonstrated that 20m could increase m6A level in intact cells. Collectively, 20m is a potent, selective and cell active ALKBH5 inhibitor and could be used as a versatile chemical probe to explore the biological function of ALKBH5.
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Desmetilasa de ARN, Homólogo 5 de AlkB , ARN , Desmetilasa de ARN, Homólogo 5 de AlkB/química , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Humanos , ARN/química , Relación Estructura-ActividadRESUMEN
Background: Ginsenoside compound K (GC-K), generated from ginseng saponins bioconverted by gut microbiota, has potential anti-colorectal cancer (CRC) effects. Meanwhile, GC-K may interact with gut microbiota, playing important roles in the occurrence and development of CRC. However, the effects of gut microbiota on the preventive and therapeutic effects of GC-K in CRC remain to be elucidated. Methods: The anti-CRC effects of GC-K were evaluated in an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated CRC Balb/c mice model under the dosage of 30 and 60 mg/kg. Stool samples were collected during the experiments for profiling gut microbiota by 16S rRNA sequencing. Correlative analysis between gut microbiota and anti-CRC effect of GC-K was also assessed. Finally, the anti-CRC effect of Akkermansia muciniphila (A. muciniphila) was validated in CRC cell lines. Results: GC-K could significantly suppress tumor growth in vivo at the dosage of 60 mg/kg without exogenous interference of gut microbiota. Moreover, dysbiosis of gut microbiota was observed in the CRC model group, which could be recovered by GC-K treatment. In particular, A. muciniphila, which could inhibit the proliferation of HCT-116, HT-29, and LOVO cells, was significantly up-regulated by GC-K. Conclusions: GC-K was verified to suppress the tumor growth of AOM/DSS-induced colitis-associated CRC through the modulation of gut microbiota, partially by up-regulation of A. muciniphila.
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Purpose: Excessive daytime sleepiness (EDS) and cerebral small vessel disease (CSVD) are common problems among older adults; however, their association is not clear. The present study aimed to investigate the frequency of EDS in CSVD patients and the relationship between EDS and neuroimaging markers of CSVD. Patients and Methods: We conducted a cross-sectional study among 1076 community-dwelling older adults aged 55-85 years. EDS was measured using the Epworth Sleepiness Scale (ESS), and EDS was defined as an ESS score greater than 10. Binary logistic regression was performed to assess the association between EDS and neuroimaging markers of CSVD. Results: Of the 1076 participants (mean age: 65.58 ± 6.46 years, 60.5% female), the prevalence of EDS was 10.0%. EDS was more frequent in participants with CSVD than in the total sample (20.0% vs 10.0%, p <0.001). In fully adjusted models, EDS was significantly correlated with CSVD burden (OR = 1.39, 95% CI 1.16 to 1.68, p <0.001), the severity of white matter hyperintensities (WMH) (OR = 1.33, 95% CI 1.14 to 1.54, p <0.001), and presence of lacunes (OR = 2.47, 95% CI 1.53 to 4.00, p <0.001) but not with the presence of cerebral microbleeds (CMBs) (OR=1.54, 95% CI 0.92 to 2.56, p = 0.099) or severity of enlarged perivascular spaces (EPVS) in basal ganglia (OR = 1.16, 95% CI 0.70 to 1.92, p = 0.564). Conclusion: We found a high frequency of EDS symptoms in CSVD individuals. Further, EDS was significantly associated with WMH, lacunes, and CSVD burden. Our findings further suggest patients with CSVD may exhibit abnormal sleep-wake patterns.
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Ataxia telangiectasia and Rad3-related (ATR) kinase is a key regulating protein within the DNA damage response (DDR), responsible for sensing replication stress (RS), and has been considered as a potential target for cancer therapy. Herein, we report the discovery of a series of 6,7-dihydro-5H-pyrrolo[3,4-d]-pyrimidine derivatives as a new class of ATR inhibitors. Among them, compound 5g exhibits an IC50 value of 0.007 µM against ATR kinase. In vitro, 5g displays good anti-tumor activity and could significantly reduce the phosphorylation level of ATR and its downstream signaling protein. Overall, this study provides a promising lead compound for subsequent drug discovery targeting ATR kinase.
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Neoplasias , Inhibidores de Proteínas Quinasas , Proteínas de la Ataxia Telangiectasia Mutada , Daño del ADN , Humanos , Neoplasias/tratamiento farmacológico , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/farmacología , Pirimidinas/uso terapéuticoRESUMEN
Aerobic glycolysis, or the Warburg effect, is regarded as a critical part of metabolic reprogramming and plays a crucial role in the occurrence and development of tumours. Ubiquitination and deubiquitination, essential post-translational modifications, have attracted increasing attention with regards to the regulation of metabolic reprogramming in cancer. However, the mechanism of ubiquitination in glycolysis remains unclear. In this review, we discuss the roles of ubiquitination and deubiquitination in regulating glycolysis, and their involvement in regulating important signalling pathways, enzymes, and transcription factors. Focusing on potential mechanisms may provide novel strategies for cancer treatment.
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Glucólisis , Neoplasias/metabolismo , Ubiquitinación , HumanosRESUMEN
BACKGROUND: Stratification of the risk of hemorrhage in patients with acute ischemic stroke following dual antiplatelet therapy (DAPT) is challenging. It remains unclear whether thromboelastography (TEG) can be used to predict DAPT-related hemorrhagic events. OBJECTIVE: The present study aims to discover predictors for hemorrhage events after DAPT based on parameters such as TEG. METHODS: A total of 859 patients with acute ischemic stroke who received DAPT were recruited consecutively. Demographic, clinical, and neuroimaging characteristics were evaluated at baseline; TEG parameters were obtained 7 days later after DAPT. Hemorrhagic events were monitored about 1 month after the stroke. RESULTS: Of the patients, 61 (7.1%) had hemorrhagic events. Patients in the hemorrhage group had a lower adenosine diphosphate (ADP)-induced platelet-fibrin clot maximum amplitude and a higher ADP inhibition rate (ADP%) than those in the non-hemorrhage group (p<0.05). ADP% was confirmed as an independent predictor of hemorrhagic events with an optimal cut-off point of 83.3% (area under the curve (AUC) = 0.665, 95% CI 0.573 to 0.767, p<0.01). We constructed a logistic model based on D-dimer, National Institutes of Health Stroke Scale scores, and ADP% to predict hemorrhagic events in patients with acute ischemic stroke during DAPT (AUC=0.720, 95% CI 0.625 to 0.858, p<0.01), with a sensitivity of 72.1% and a specificity of 76.5%. CONCLUSIONS: Monitoring changes of TEG parameters helps to guide personalized DAPT for patients with ischemic stroke. A 30-82.3% range of ADP% is recommended for DAPT treatment.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adenosina Difosfato/farmacología , Quimioterapia Combinada , Hemorragia/inducido químicamente , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Tromboelastografía , Resultado del TratamientoRESUMEN
KEY MESSAGE: Expression of Cre recombinase by AtRps5apro or AtDD45pro enabled Cre/lox-mediated recombination at an early embryonic developmental stage upon crossing, activating transgenes in the hybrid cowpea and tobacco. Genetic engineering ideally results in precise spatiotemporal control of transgene expression. To activate transgenes exclusively in a hybrid upon fertilization, we evaluated a Cre/lox-mediated gene activation system with the Cre recombinase expressed by either AtRps5a or AtDD45 promoters that showed activity in egg cells and young embryos. In crosses between Cre recombinase lines and transgenic lines harboring a lox-excision reporter cassette with ZsGreen driven by the AtUbq3 promoter after Cre/lox-mediated recombination, we observed complete excision of the lox-flanked intervening DNA sequence between the AtUbq3pro and the ZsGreen coding sequence in F1 progeny upon genotyping but no ZsGreen expression in F1 seeds or seedlings. The incapability to observe ZsGreen fluorescence was attributed to the activity of the AtUbq3pro. Strong ZsGreen expression in F1 seeds was observed after recombination when ZsGreen was driven by the AtUbq10 promoter. Using the AtDD45pro to express Cre resulted in more variation in recombination frequencies between transgenic lines and crosses. Regardless of the promoter used to regulate Cre, mosaic F1 progeny were rare, suggesting gene activation at an early embryo-developmental stage. Observation of ZsGreen-expressing tobacco embryos at the globular stage from crosses with the AtRps5aproCre lines pollinated by the AtUbq3prolox line supported the early activation mode.
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Genes de Plantas , Integrasas/genética , Proteínas de Plantas/genética , Activación Transcripcional , Transgenes , Vigna/genética , Integrasas/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Vigna/enzimologíaRESUMEN
Objectives: Diabetes mellitus (DM) is a significant risk factor for ischemic stroke and associated with platelet reactivity. We aim to evaluate the effect of DM on platelet function in acute ischemic stroke patients taking dual antiplatelet therapy (DAPT). Methods: We consecutively included patients with acute ischemic stroke taking DAPT. Platelet function was assessed by thromboelastography and the arachidonic acid (AA) or adenosine diphosphate (ADP) induced platelet inhibition rate were used to confirmed the high-residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel. We classified patients into DM and non-DM groups. The association between DM and platelet function was assessed and the confounding factors were adjusted by propensity score matching (PSM) analysis. The independent risk factors of HRPR were determined by multivariate logistic regression analysis. Results: A total of 1,071 acute ischemic stroke patients, 712 in the non-DM group and 359 in the DM group, were included. Patients with DM had a significantly higher maximum amplitude (63.0 vs. 62.0 mm, P < 0.01), ADP-induced clot strength (34.6 vs. 30.3 mm, P < 0.01) and clopidogrel HRPR rate (22.6% vs. 17.3%, P = 0.038) than those without DM. Among 662 patients after PSM, the maximum amplitude (63.1 vs. 62.5 mm, P = 0.032), ADP-induced clot strength (34.6 vs. 29.3 mm, P < 0.01) and clopidogrel HRPR rate (23.0% vs. 15.7%, P = 0.018) is still higher in the DM group. DM was an independent factor of clopidogrel HRPR (OR = 1.48, 95% CI: 1.03-2.07, P < 0.05). Conclusions: In acute ischemic stroke patients taking DAPT, DM is associated with increased platelet reactivity and higher prevalence of clopidogrel HRPR.
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Background: Physical frailty is a common problem among older adults which usually leads to adverse health outcomes. The imaging markers of cerebral small vessel disease (CSVD) are associated with frailty, but the underlying mechanisms remain unclear. The present study aimed to investigate the mediating role of sleep quality in the relationship between CSVD burden and frailty. Methods: We performed a cross-sectional study and enrolled community residents. Frailty and sleep quality were measured using the Fried frailty phenotype and the Pittsburgh Sleep Quality Index (PSQI), respectively. A multivariate linear regression analysis and a Bootstrap analysis were performed to examine the association among the key variables and the mediating role of sleep quality. Results: Of the 726 participants (mean age: 65.5 ± 6.5 years, 59.8% female), the numbers (percentages) of the frail, prefrail, and robust residents were 49 (6.7%), 310 (42.7%), and 367 (50.6%), respectively. After adjusting for covariates, the CSVD burden and PSQI score were significantly associated with the frailty score. In addition, sleep quality played a partial mediating role in the association between CSVD burden and physical frailty. The mediating effect was 21.9%. Conclusion: The present study suggests that sleep quality is a mediator of this association between CSVD and frailty in community-dwelling older adults. Improving sleep quality might be helpful to mitigate the risk of frailty in CSVD patients.
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Background and Purpose: In-stent restenosis (ISR) after carotid artery stent (CAS) is not uncommon. We aimed to evaluate therapeutic options for ISR after CAS. Methods: We searched PubMed and EMBASE until November 2, 2020 for studies including the treatment for ISR after CAS. Results: In total, 35 studies, covering 1,374 procedures in 1,359 patients, were included in this review. Most cases (66.3%) were treated with repeat CAS (rCAS), followed by percutaneous transluminal angioplasty (PTA) (17.5%), carotid endarterectomy (CEA) (14.3%), carotid artery bypass (1.5%), and external beam radiotherapy (0.4%). The rates of stroke & TIA within the postoperative period were similar in three groups (PTA 1.1%, rCAS 1.1%, CEA 1.5%). CEA (2.5%) was associated with a slightly higher rate of postoperative death than rCAS (0.7%, P = 0.046). Furthermore, the rate of long-term stroke & TIA in PTA was 5.7%, significantly higher than rCAS (1.8%, P = 0.036). PTA (27.8%) was also associated with a significantly higher recurrent restenosis rate than rCAS (8.2%, P = 0.002) and CEA (1.6%, P < 0.001). The long-term stroke & TIA and recurrent restenosis rates showed no significant difference between rCAS and CEA. Conclusions: rCAS is the most common treatment for ISR, with low postoperative risk and low long-term risk. CEA is an important alternative for rCAS. PTA may be less recommended due to the relatively high long-term risks of stroke & TIA and recurrent restenosis.