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Growing evidence suggests that systemic immune and inflammatory responses may play a critical role in the formation and development of aneurysms. Exploring the differences between single intracranial aneurysm (SIA) and multiple IAs (MIAs) could provide insights for targeted therapies. However, there is a lack of comprehensive and detailed characterization of changes in circulating immune cells in MIAs. Peripheral blood mononuclear cell (PBMC) samples from patients with SIA (n = 16) or MIAs (n = 6) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. A total of 25 cell clusters were identified, revealing that the immune signature of MIAs included cluster changes. Compared to patients with SIA, patients with MIAs exhibited immune dysfunction and regulatory imbalance in T-cell clusters. They also had reduced numbers of CD8+ T cells and their subgroups CD8+ Te and CD8+ Tem cells, as well as reduced numbers of the CD4+ T-cell subgroup CD27-CD4+ Tem cells. Furthermore, compared to SIA, MIAs were associated with enhanced T-cell immune activation, with elevated expression levels of CD3, CD25, CD27, CCR7, GP130, and interleukin 10. This study provides insights into the circulating immune cell profiles in patients with MIAs, highlighting the similarities and differences between patients with SIA and those with MIAs. Furthermore, the study suggests that circulating immune dysfunction may contribute to development of MIAs.
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BACKGROUND: The study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and ischemic stroke events after revascularization in patients with Moyamoya disease (MMD). METHODS: This study prospectively enrolled 275 MMD patients from September 2020 to December 2021. Patients with alcoholism and other liver diseases were excluded. NAFLD was confirmed by CT imaging or abdominal ultrasonography. Stroke events and modified Rankin Scale (mRS) scores at the latest follow-up were compared between the two groups. RESULTS: A total of 275 patients were enrolled in the study, among which 65 were diagnosed with NAFLD. Univariate logistic regression analysis showed that NAFLD (P = 0.029) was related to stroke events. Multivariate logistic regression analysis showed that NAFLD is a predictor of postoperative stroke in MMD patients (OR = 27.145, 95% CI = 2.031-362.81, P = 0.013). Kaplan-Meier analysis showed that compared with MMD patients with NAFLD, patients in the control group had a longer stroke-free time (P = 0.004). Univariate Cox analysis showed that NAFLD (P = 0.016) was associated with ischemic stroke during follow-up in patients with MMD. Multivariate Cox analysis showed that NAFLD was an independent risk factor for stroke in patients with MMD (HR = 10.815, 95% CI = 1.259-92.881, P = 0.030). Furthermore, fewer patients in the NAFLD group had good neurologic status (mRS score ≤ 2) than the control group (P = 0.005). CONCLUSION: NAFLD was an independent risk factor for stroke in patients with MMD after revascularization and worse neurological function outcomes.
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Revascularización Cerebral , Accidente Cerebrovascular Isquémico , Enfermedad de Moyamoya , Enfermedad del Hígado Graso no Alcohólico , Accidente Cerebrovascular , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Estudios Prospectivos , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/cirugía , Resultado del Tratamiento , Revascularización Cerebral/efectos adversos , Revascularización Cerebral/métodos , Accidente Cerebrovascular/complicaciones , Factores de Riesgo , Estudios RetrospectivosRESUMEN
The progress from intelligent interactions and supplemented/augmented reality requires artificial skins to shift from the single-functional tactile paradigm. Dual-responsive sensors that can both detect pre-contact proximal events and tactile pressure levels enrich the perception dimensions and deliver additional cognitive information. Previous dual-responsive sensors show very limited utilizations only in proximity perception or approaching switches. Whereas, the approaching inputs from the environment should be able to convey more valuable messages. Herein, a flexible iontronic dual-responsive artificial skin is present. The artificial skin is sensitive to external object's applied pressure as well as its approaching, and can elicit information of target material categories encoded in the proximal inputs. Versatile applications are then demonstrated. Dual-mode human-machine interfaces are developed based on the devices, including a manipulation of virtual game characters, navigation and zooming in of electronic maps, and scrolling through electronic documents. More importantly, the proof-of-concept application of an entirely touchless material classification system is demonstrated. Three types of materials (metals, polymers, and human skins) are classified and predicted accurately. These features of the artificial skin make it highly promising for next-generation smart engineered electronics.
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Piel Artificial , Dispositivos Electrónicos Vestibles , Humanos , Tacto , Piel , ElectrónicaRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.
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Aneurisma de la Aorta Abdominal/cirugía , Rotura de la Aorta/cirugía , COVID-19/prevención & control , Infección Hospitalaria/prevención & control , Control de Infecciones , Procedimientos Quirúrgicos Vasculares , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico , Rotura de la Aorta/diagnóstico , COVID-19/diagnóstico , COVID-19/transmisión , COVID-19/virología , Prueba de COVID-19 , China , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/transmisión , Infección Hospitalaria/virología , Urgencias Médicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Flujo de TrabajoRESUMEN
Here we propose an inverted evanescently-coupled waveguide modified uni-traveling-carrier photodiode (IECWG MUTC-PD) and verify the character numerically. In this photodiode, the epitaxial structure is inverted from p-i-n to n-i-p, and a diluted waveguide is applied. The material of capacitance control layer is optimized to realize energy band compensation and capacitance control. Such structure possesses a large electric field in the whole depletion region and has a uniform light absorption, which improves the space charge effect. As a result, the PD achieves a 3-dB bandwidth of 71.9 GHz with a 35µm2 active area at -5V bias voltage and an internal responsivity of 0.59 A/W in 7-µm long short PD with a 200-nm-thick absorption layer.
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Biological organisms often have remarkable multifunctionality through intricate structures, such as concurrent shape morphing and stiffness variation in the octopus. Soft robots, which are inspired by natural creatures, usually require the integration of separate modules to achieve these various functions. As a result, the whole structure is cumbersome, and the control system is complex, often involving multiple control loops to finish a required task. Here, inspired by the scales that cover creatures like pangolins and fish, we developed a robotic structure that can vary its stiffness and change shape simultaneously in a highly integrated, compact body. The scale-inspired layered structure (SAILS) was enabled by the inversely designed programmable surface patterns of the scales. After fabrication, SAILS was inherently soft and flexible. When sealed in an elastic envelope and subjected to negative confining pressure, it transitioned to its designated shape and concurrently became stiff. SAILS could be actuated at frequencies as high as 5 hertz and achieved an apparent bending modulus change of up to 53 times between its soft and stiff states. We further demonstrated both the versatility of SAILS by developing a soft robot that is amphibious and adaptive and tunable landing systems for drones with the capacity to accommodate different loads.
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Image retrieval performance can be improved by training a convolutional neural network (CNN) model with annotated data to facilitate accurate localization of target regions. However, obtaining sufficiently annotated data is expensive and impractical in real settings. It is challenging to achieve accurate localization of target regions in an unsupervised manner. To address this problem, we propose a new unsupervised image retrieval method named unsupervised target region localization (UTRL) descriptors. It can precisely locate target regions without supervisory information or learning. Our method contains three highlights: 1) we propose a novel zero-label transfer learning method to address the problem of co-localization in target regions. This enhances the potential localization ability of pretrained CNN models through a zero-label data-driven approach; 2) we propose a multiscale attention accumulation method to accurately extract distinguishable target features. It distinguishes the importance of features by using local Gaussian weights; and 3) we propose a simple yet effective method to reduce vector dimensionality, named twice-PCA-whitening (TPW), which reduces the performance degradation caused by feature compression. Notably, TPW is a robust and general method that can be widely applied to image retrieval tasks to improve retrieval performance. This work also facilitates the development of image retrieval based on short vector features. Extensive experiments on six popular benchmark datasets demonstrate that our method achieves about 7% greater mean average precision (mAP) compared to existing state-of-the-art unsupervised methods.
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Moyamoya disease (MMD) is a rare, chronic, and progressive cerebrovascular disorder with unclear underlying causes and mechanisms. Previous studies suggest a potential involvement of endothelial-mesenchymal transition (EndMT) in the pathogenesis of MMD. This study aimed to explore the contribution of EndMT-related genes (ERGs) in MMD. Two datasets, GSE141022 and GSE157628, were integrated as the training set after batch effects removal. Differentially expressed ERGs were identified between MMD and control groups. Functional enrichment analysis and immune infiltration analysis were further performed. LASSO regression was used for hub MMD-related ERG selection. Consensus clustering was used for MMD subtype classification based on these hub MMD-related ERGs. Molecular characteristics between MMD subtypes were analyzed using WGCNA. PPI network was used to illuminate the genetic relationship. The hub MMD-related ERGs were validated in an independent testing set, GSE189993. The nomogram model was constructed and evaluated using ROC curves and calibration plots. Additionally, CCK-8, EdU, wound healing, and western blot were performed to confirm the function of the hub MMD-related ERGs. A total of 107 DE-ERGs were identified. Functional enrichment analysis showed these genes were associated with EndMT and immune response. The infiltrating levels of immune cells were commonly higher in the MMD group. LASSO regression identified 12 hub MMD-related ERGs, leading to the identification of two MMD subtypes. Four ERGs emerged as the final hub MMD-related ERGs after validation in the testing set, including CCL21, CEBPA, KRT18, and TNFRSF11A. The nomogram model exhibited excellent discrimination ability. In vitro experiments showed that CCL21, CEBPA, KRT18, and TNFRSF11A could promote proliferation, migration, and EndMT. This study investigated the potential role of EndMT in MMD and identified four hub MMD-related ERGs, providing potential therapeutic targets for MMD treatment.
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Moyamoya disease (MMD) is a cerebrovascular disorder marked by progressive arterial narrowing, categorized into six stages known as Suzuki stages based on angiographic features. Growing evidence indicates a pivotal role of systemic immune and inflammatory responses in the initiation and advancement of MMD. This study employs high-dimensional mass cytometry to reveal the immunophenotypic characteristics of peripheral blood immune cells (PBMCs) at various Suzuki stages, offering insights into the progression of MMD. PBMC samples from eight patients with early-stage MMD (Suzuki stages II and III) and eight patients with later-stage MMD (Suzuki stages IV, V, and VI) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. We identified 15 cell clusters and found that the immunological features of early-stage MMD and later-stage MMD are composed of cluster variations. In this study, we confirmed that, compared to later-stage MMD, the early-stage MMD group exhibits an increase in non-classical monocytes. As the Suzuki stage level increases, the proportions of plasmacytoid DCs and monocyte-derived DCs decrease. Furthermore, T cells, monocytes, DCs, and PMN-MDSCs in the early-stage MMD group show activation of the canonical NF-κB signaling pathway. We summarized and compared the similarities and differences between early-stage MMD patients and later-stage MMD patients. There is a potential role of circulating immune dysfunction and inflammatory responses in the onset and development of MMD.
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Inmunofenotipificación , Enfermedad de Moyamoya , Humanos , Enfermedad de Moyamoya/inmunología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Citometría de Flujo , Células Dendríticas/inmunología , Leucocitos Mononucleares/inmunología , FN-kappa B/metabolismo , Linfocitos T/inmunología , Progresión de la Enfermedad , Monocitos/inmunología , Transducción de Señal/inmunología , Adolescente , Adulto JovenRESUMEN
At present, there is limited research on the mechanisms underlying moyamoya disease (MMD). Herein, we aimed to determine the role of glutamine in MMD pathogenesis, and 360 adult patients were prospectively enrolled. Human brain microvascular endothelial cells (HBMECs) were subjected to Integrin Subunit Beta 4 (ITGB4) overexpression or knockdown and atorvastatin. We assessed factors associated with various signaling pathways in the context of the endothelial-to-mesenchymal transition (EndMT), and the expression level of related proteins was validated in the superficial temporal arteries of patients. We found glutamine levels were positively associated with a greater risk of stroke (OR = 1.599, p = 0.022). After treatment with glutamine, HBMECs exhibited enhanced proliferation, migration, and EndMT, all reversed by ITGB4 knockdown. In ITGB4-transfected HBMECs, the MAPK-ERK-TGF-ß/BMP pathway was activated, with Smad4 knockdown reversing the EndMT. Furthermore, atorvastatin suppressed the EndMT by inhibiting Smad1/5 phosphorylation and promoting Smad4 ubiquitination in ITGB4-transfected HBMECs. We also found the protein level of ITGB4 was upregulated in the superficial temporal arteries of patients with MMD. In conclusion, our study suggests that glutamine may be an independent risk factor for hemorrhage or infarction in patients with MMD and targeting ITGB4 could potentially be therapeutic approaches for MMD.
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BACKGROUND: Moyamoya disease (MMD) stands as a prominent cause of stroke among children and adolescents in East Asian populations. Although a growing body of evidence suggests that dysregulated inflammation and autoimmune responses might contribute to the development of MMD, a comprehensive and detailed understanding of the alterations in circulating immune cells associated with MMD remains elusive. METHODS: In this study, we employed a combination of single-cell RNA sequencing (scRNA-seq), mass cytometry and RNA-sequencing techniques to compare immune cell profiles in peripheral blood samples obtained from patients with MMD and age-matched healthy controls. RESULTS: Our investigation unveiled immune dysfunction in MMD patients, primarily characterized by perturbations in T-cell (TC) subpopulations, including a reduction in effector TCs and an increase in regulatory TCs (Tregs). Additionally, we observed diminished natural killer cells and dendritic cells alongside heightened B cells and monocytes in MMD patients. Notably, within the MMD group, there was an augmented proportion of fragile Tregs, whereas the stable Treg fraction decreased. MMD was also linked to heightened immune activation, as evidenced by elevated expression levels of HLA-DR and p-STAT3. CONCLUSIONS: Our findings offer a comprehensive view of the circulating immune cell landscape in MMD patients. Immune dysregulation in patients with MMD was characterized by alterations in T-cell populations, including a decrease in effector T-cells and an increase in regulatory T-cells (Tregs), suggest a potential role for disrupted circulating immunity in the aetiology of MMD.
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Enfermedad de Moyamoya , Niño , Adolescente , Humanos , Enfermedad de Moyamoya/genética , Enfermedad de Moyamoya/metabolismo , Inflamación , Linfocitos T Reguladores/metabolismoRESUMEN
BACKGROUND: Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. METHODS: The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. CONCLUSIONS: The MOYAOMICS project represents a significant step toward comprehending MMD's molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.
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Coalbed methane is a type of high-quality clean energy. The development of coalbed methane helps protect the living environment of humans and solves the safety problems in coal mining. However, a large amount of pulverized coal is generated after coalbed methane fracturing, which reduces the production of coalbed methane. Reduction of pulverized coal generation and prevention of pulverized coal migration are important for the development of coalbed methane. This study innovatively mixed calcium sulfoaluminate particles and sand to create a new fracturing proppant. The new proppant was carried by the fracturing fluid into the formation cracks and cured to form a permeable cement stone with a certain compressive strength and permeability at formation temperature and pressure. The permeability and compressive strength of the permeable cement stone were measured at different curing temperatures. Results showed that when the compressive strength of the permeable cement stone was 5.46 MPa, the gas and water permeabilities could reach 2.06 and 0.57 D, respectively. The pore diameter distribution was measured with the semi-permeable diaphragm method. The distribution curve was bimodal, and the range of the variation in pore size was 0.6-300 µm. Blocked pulverized coal size was determined using the seepage theory of particles in porous media and verified through a pulverized coal control experiment. Pulverized coal with a diameter larger than 7.67 µm was blocked by the permeable cement stone. The efficiency of the permeable cement stone in controlling pulverized coal could reach 96%. This study proved that calcium sulfoaluminate cementitious proppants can fix pulverized coal and prevent its migration. It also provided the compressive strength of propping fractures and the high permeability needed for drainage under formation conditions.
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To improve the resistance to CO2 corrosion of oil well cement, soap-free emulsion polymerization was used to prepare a soap-free latex (PSAC) with sodium styrene sulfonate (SSS) and nano-SiO2 (SSS/SiO2) as the ionic copolymer emulsifier. The effects of SSS/SiO2 on the performance, thermal stability, and latex particle morphology of the PSAC were investigated through zeta potential, TGA, and TEM measurements, respectively. The carbonation resistance properties of cement with PSAC were evaluated, and the anticorrosion mechanism of the PSAC cement was determined by SEM, EDS, XRD, and 29Si NMR analyses. The results showed that the PSAC particle size was uniform, the particles were monodispersed, and they had a typical core-shell structure and good heat resistance. The carbonation resistance test results showed that after 60 days of corrosion, the corrosion depth of the cement with 12.0% PSAC content was only 2.16 mm, the permeability was 0.0018 mD, and the decrease in the compressive strength was 6.65%. The porosity in the cement was reduced significantly, and the pore volume (>50 nm) of the cement was reduced by 0.24 times. The PSAC film formation decreased the contact between hydration products and CO2. In addition, the nano-SiO2 in the PSAC reacted with Ca(OH)2 to reduce the free Ca(OH)2 content in the cement and generate C-S-H gel with a low Ca/Si ratio and high polymerization, which did not react as readily with CO2.