Circulating immune cell landscape and T-cell abnormalities in patients with moyamoya disease.

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.

High glutamine increases stroke risk by inducing the endothelial-to-mesenchymal transition in moyamoya disease.

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.

Locating Target Regions for Image Retrieval in an Unsupervised Manner.

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.

Nonalcoholic fatty liver disease is an independent risk factor for ischemic stroke after revascularization in patients with Moyamoya disease: a prospective cohort study.

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.

Mass cytometry revealed the circulating immune cell landscape across different Suzuki stages of Moyamoya disease.

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.

Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS).

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.

A Dual-Responsive Artificial Skin for Tactile and Touchless Interfaces.

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.

Investigation on Pulverized Coal Control Using Calcium Sulfoaluminate Cementitious Proppants in Coalbed Methane Fracturing.

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.

Managing Emergent Surgery for Ruptured Abdominal Aortic Aneurysm during the COVID-19 Pandemic.

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.

High-performance inverted evanescently coupled waveguide integrated MUTC-PD with high response speed.

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.

Study on the Preparation and Anti-CO2 Corrosion Performance of Soap-Free Latex for Oil Well Cement.

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.