40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice.

The glymphatic-lymphatic system is increasingly recognized as fundamental for the homeostasis of the brain milieu since it defines cerebral spinal fluid flow in the brain parenchyma and eliminates metabolic waste. Animal and human studies have uncovered several important physiological factors regulating the glymphatic system including sleep, aquaporin-4, and hemodynamic factors. Yet, our understanding of the modulation of the glymphatic system is limited, which has hindered the development of glymphatic-based treatment for aging and neurodegenerative disorders. Here, we present the evidence from fluorescence tracing, two-photon recording, and dynamic contrast-enhanced magnetic resonance imaging analyses that 40 Hz light flickering enhanced glymphatic influx and efflux independently of anesthesia and sleep, an effect attributed to increased astrocytic aquaporin-4 polarization and enhanced vasomotion. Adenosine-A2A receptor (A2AR) signaling emerged as the neurochemical underpinning of 40 Hz flickering-induced enhancement of glymphatic flow, based on increased cerebrofluid adenosine levels, the abolishment of enhanced glymphatic flow by pharmacological or genetic inactivation of equilibrative nucleotide transporters-2 or of A2AR, and by the physical and functional A2AR-aquaporin-4 interaction in astrocytes. These findings establish 40 Hz light flickering as a novel non-invasive strategy of enhanced glymphatic flow, with translational potential to relieve brain disorders.

Association between dietary fiber intake and kidney stones: results from the National Health and Nutrition Examination Survey (2011-2018).

BACKGROUND/OBJECTIVES: Studies on the impact of dietary fiber intake on kidney stones are few, and their results were controversial. This study aimed to explore the association between dietary fiber intake and kidney stones in the nationally representative population of the USA. SUBJECTS/METHODS: This cross-sectional research included 8,588 participants from the National Health and Nutrition Examination Survey, 2011 to 2018. Information regarding dietary fiber intake was obtained from a 24-h recall survey. Participants were categorized into different dietary fiber intake tertiles according to the average of 2 days of dietary recall data. The outcome was self-reported kidney stones. After adjusting for the traditional risk factors, a multivariate logistic regression model was used to examine the association between dietary fiber intake and kidney stones. RESULTS: Eight hundred seventy-two participants had kidney stones. The weighted prevalence (SE) of kidney stones in the lowest tertile, medium tertile, and highest tertile of dietary fiber intake was 11.8% (0.8%), 10.3% (0.8%), and 9.1% (0.8%), respectively. After adjusting for age, sex, race and ethnicity, education level, smoking status, alcohol consumption, physical activity, body mass index, hypertension, diabetes, dyslipidemia, daily water intake, chronic kidney disease stage 3-5, and total energy intake, participants with the highest tertile of fiber intake had a significantly lower risk of kidney stones (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.48-0.95) compared to those in the lowest tertile. Every 5 g/day increment in dietary fiber intake was associated with a significant decrease in risk of kidney stones (OR, 0.90; 95% CI, 0.83-0.98). CONCLUSION: An increase in dietary fiber intake was associated with a lower risk of kidney stones, suggesting adults should be encouraged to maintain an adequate dietary fiber intake to prevent the development of kidney stones. Our results provide evidence to formulate nutrition management strategies for the prevention of kidney stones.

Portable ultrasound-guided keyhole evacuation of intracerebral hemorrhage: a detailed case report highlighting technical nuances.

Intracerebral hemorrhage (ICH) is a common neurosurgical emergency that is associated with high morbidity and mortality. Minimally invasive or endoscopic hematoma evacuation has emerged in recent years as a viable alternative to conventional large craniotomies. However, accurate trajectory planning and placement of the tubular retractor remains a challenge. We describe a novel technique for handheld portable ultrasound-guided minimally invasive endoscopic evacuation of supratentorial hematomas. A 64-year-old male diagnosed right hematoma (48.5 mL) at the basal ganglia was treated with emergent ultrasound-guided endoscopic transtubular evacuation through a small craniotomy. Ultrasound-guidance facilitated optimal placement of the tubular retractor into the long axis of the hematoma, and allowed for near-total evacuation, reducing iatrogenic tissue damage by mitigating the need for wanding or repositioning of the retractor. The emergence of a new generation of small portable phased array ultrasound probes with improved resolution and clarity has broadened ultrasound's clinical applications.

Comprehensive molecular characterization of collecting duct carcinoma for therapeutic vulnerability.

Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

Spatio-temporal evolution characteristics and driving mechanisms of waterlogging in urban agglomeration from multi-scale perspective: A case study of the Guangdong-Hong Kong-Macao Greater Bay Area, China.

Understanding the characteristics of waterlogging in urban agglomeration is essential for effective waterlogging prevention and management, as well as for promoting sustainable urban development. Previous studies have predominantly focused on the driving mechanisms of waterlogging in urban agglomeration at a single scale, but urban agglomeration space has greater spatio-temporal heterogeneity, it is often difficult to fully reveal such characteristics at a single scale. Consequently, this study endeavors to explore the spatio-temporal evolution characteristics and underlying mechanisms of waterlogging incidents within urban agglomerations by adopting a multi-scale analytical approach. The results indicate that: (1) The waterlogging degree and high-density zones increase in the GBA, and the waterlogging points are spatially polycentric. However, the waterlogging point in Hong Kong is decreasing. (2) The influence of ISP and AI on waterlogging is dominant at all scales, followed by RE and Slope. ISP∩Slope and ISP∩RE are the key interactions for waterlogging. (3) The aggregation of waterlogging decreases with grid scale, and the influence of land cover factors on waterlogging increases with grid scale. Moreover, the findings at the grid scale outperformed those at the watershed scale, indicating that the grid scale is more conducive to the investigation of waterlogging in urban agglomerations. This research broadens our comprehension of the mechanisms behind waterlogging in urban agglomeration and provide references for policy decisions on waterlogging prevention and mitigation within urban agglomerations.

Chromosome-level assembly of Lindenbergia philippensis and comparative genomic analyses shed light on genome evolution in Lamiales.

Lamiales, comprising over 23,755 species across 24 families, stands as a highly diverse and prolific plant group, playing a significant role in the cultivation of horticultural, ornamental, and medicinal plant varieties. Whole-genome duplication (WGD) and its subsequent post-polyploid diploidization (PPD) process represent the most drastic type of karyotype evolution, injecting significant potential for promoting the diversity of this lineage. However, polyploidization histories, as well as genome and subgenome fractionation following WGD events in Lamiales species, are still not well investigated. In this study, we constructed a chromosome-level genome assembly of Lindenbergia philippensis (Orobanchaceae) and conducted comparative genomic analyses with 14 other Lamiales species. L. philippensis is positioned closest to the parasitic lineage within Orobanchaceae and has a conserved karyotype. Through a combination of Ks analysis and syntenic depth analysis, we reconstructed and validated polyploidization histories of Lamiales species. Our results indicated that Primulina huaijiensis underwent three rounds of diploidization events following the γ-WGT event, rather than two rounds as reported. Besides, we reconfirmed that most Lamiales species shared a common diploidization event (L-WGD). Subsequently, we constructed the Lamiales Ancestral Karyotype (LAK), comprising 11 proto-chromosomes, and elucidated its evolutionary trajectory, highlighting the highly flexible reshuffling of the Lamiales paleogenome. We identified biased fractionation of subgenomes following the L-WGD event across eight species, and highlighted the positive impacts of non-WGD genes on gene family expansion. This study provides novel genomic resources and insights into polyploidy and karyotype remodeling of Lamiales species, essential for advancing our understanding of species diversification and genome evolution.

A hybrid quantum-classical classification model based on branching multi-scale entanglement renormalization ansatz.

Tensor networks are emerging architectures for implementing quantum classification models. The branching multi-scale entanglement renormalization ansatz (BMERA) is a tensor network known for its enhanced entanglement properties. This paper introduces a hybrid quantum-classical classification model based on BMERA and explores the correlation between circuit layout, expressiveness, and classification accuracy. Additionally, we present an autodifferentiation method for computing the cost function gradient, which serves as a viable option for other hybrid quantum-classical models. Through numerical experiments, we demonstrate the accuracy and robustness of our classification model in tasks such as image recognition and cluster excitation discrimination, offering a novel approach for designing quantum classification models.

Association between dietary fiber intake and peripheral artery disease in hypertensive patients.

BACKGROUND: At present, no studies explored whether dietary fiber intake was associated with the risk of peripheral artery disease (PAD) in hypertensive patients. This study assessed the association between dietary fiber intake and PAD in hypertensive patients. METHODS: This cross-sectional study collected the data of 4628 participants with the measurement of ankle-brachial pressure index in the National Health and Nutrition Examination Surveys database. Univariate logistic regression analysis was applied to identify variables associated with PAD as confounding factors. Univariate and multivariable logistic regression analyses were used to explore the association between dietary fiber intake and PAD in hypertensive patients. Subgroup analysis was stratified by age, cardiovascular disease, dyslipidemia, diabetes, smoking, and physical activity. RESULTS: After adjusting for confounding factors, decreased risk of PAD was observed in hypertensive patients with dietary fiber intake > 21 g [odds ratio (OR) = 0.67, 95% confidence interval (CI) 0.46-0.99]. Compared with people with dietary fiber intake ≤ 21 g, those with dietary fiber intake > 21 g were associated with decreased risk of PAD in hypertensive patients < 60 years (OR = 0.23, 95%CI 0.08-0.66). In hypertensive patients without dyslipidemia, dietary fiber intake > 21 g were associated with reduced risk of PAD (OR = 0.33, 95%CI 0.12-0.95). Decreased risk of PAD was also found in hypertensive patients without diabetes in dietary fiber intake > 21 g group (OR = 0.50, 95%CI 0.31-0.78). Dietary fiber intake > 21 g was linked with reduced risk of PAD in hypertensive patients in never smoke group (OR = 0.46, 95%CI 0.24-0.86). CONCLUSION: Higher dietary fiber intake was associated with reduced risk of PAD in hypertensive patients, suggesting the importance of increase the daily dietary quality especially fiber intake in hypertensive people.

End-to-End Autonomous Driving Decision Method Based on Improved TD3 Algorithm in Complex Scenarios.

The ability to make informed decisions in complex scenarios is crucial for intelligent automotive systems. Traditional expert rules and other methods often fall short in complex contexts. Recently, reinforcement learning has garnered significant attention due to its superior decision-making capabilities. However, there exists the phenomenon of inaccurate target network estimation, which limits its decision-making ability in complex scenarios. This paper mainly focuses on the study of the underestimation phenomenon, and proposes an end-to-end autonomous driving decision-making method based on an improved TD3 algorithm. This method employs a forward camera to capture data. By introducing a new critic network to form a triple-critic structure and combining it with the target maximization operation, the underestimation problem in the TD3 algorithm is solved. Subsequently, the multi-timestep averaging method is used to address the policy instability caused by the new single critic. In addition, this paper uses Carla platform to construct multi-vehicle unprotected left turn and congested lane-center driving scenarios and verifies the algorithm. The results demonstrate that our method surpasses baseline DDPG and TD3 algorithms in aspects such as convergence speed, estimation accuracy, and policy stability.

Astrocytic pyruvate dehydrogenase kinase-lactic acid axis involvement in glia-neuron crosstalk contributes to morphine-induced hyperalgesia in mice.

The activation of spinal astrocytes accounts for opioid-induced hyperalgesia (OIH), but the underlying mechanisms remain elusive. The presence of astrocyte-neuron lactate shuttle (ANLS) makes astrocytes necessary for some neural function and communication. The aim of this study was to explore the role of ANLS in the occurrence and maintenance of OIH. After 7 days consecutive morphine injection, a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4 (PDK4), phosphorylated pyruvate dehydrogenase (p-PDH) and accumulation of L-lactate was elevated in the spinal dorsal horn. Intrathecally administration of inhibitors of PDK, lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal horns. The astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in vitro. In this study, we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal ANLS. In this process, PDK-p-PDH-lactate axis serves a pivotal role, which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.

Spray performance simulation and experiment analysis of a greenhouse fixed-pipe twin-fluid cold fogger with different nozzle settings.

BACKGROUND: High-efficient pesticide application equipment for protected cultivation is scarce. In response, a fixed-pipe twin-fluid clod fogger (FTCF) was proposed as a potential solution. To investigate the optimal nozzle layout and spray performance, a computational fluid dynamics (CFD) model was used to study the airflow distribution and spray deposition of a FTCF with different nozzle settings using the Euler-Lagrange approach. Specifically, two piping configurations, middle-cross-inverted (MCI) and bilateral-malposed-opposite (BMO), were combined with three nozzle spacings (2 m, 3 m, 4 m) resulting in six nozzle settings. Additionally, a greenhouse spray trial was conducted to test the performance of FTCF with the selected nozzle settings and to validate the model. RESULTS: The simulation results revealed that MCI piping configuration exhibited a stronger airflow disturbance compared to BMO configuration, indicating a more significant air-guided effect in the MCI configuration. Combining this finding with the ground droplet distribution analysis of MCI piping configuration, it was observed that MCI-2 m had the lowest coefficient of variation (CV) for ground deposition (20.56%). Consequently, MCI-2 m was determined as the most optimal nozzle setting. Verification results demonstrated a high consistency between experimental and simulated spray deposition results. CONCLUSIONS: The FTCF system effectively generated a three-dimensional airflow field throughout the greenhouse environment. Furthermore, jet flow produced by FTCF disrupted the overall airflow pattern within the greenhouse space which facilitated droplet suspension and dispersion. This study provides valuable insights and innovative ideas for enhancing pesticide application technologies in protected cultivations. © 2024 Society of Chemical Industry.

A Calibration Strategy for Silicon Nanowire Field-Effect Transistor Biosensors and Its Application in Ultra-Sensitive, Label-Free Biosensing.

The silicon nanowire field-effect transistor (SiNW FET) has been developed for over two decades as an ultrasensitive, label-free biosensor for biodetection. However, inconsistencies in manufacturing and surface functionalization at the nanoscale have led to poor sensor-to-sensor consistency in performance. Despite extensive efforts to address this issue through process improvements and calibration methods, the outcomes have not been satisfactory. Herein, based on the strong correlation between the saturation response of SiNW FET biosensors and both their feature size and surface functionalization, we propose a calibration strategy that combines the sensing principles of SiNW FET with the Langmuir-Freundlich model. By normalizing the response of the SiNW FET biosensors (ΔI/I0) with their saturation response (ΔI/I0)max, this strategy fundamentally overcomes the issues mentioned above. It has enabled label-free detection of nucleic acids, proteins, and exosomes within 5 min, achieving detection limits as low as attomoles and demonstrating a significant reduction in the coefficient of variation. Notably, the nucleic acid test results exhibit a strong correlation with the ultraviolet-visible (UV-vis) spectrophotometer measurements, with a correlation coefficient reaching 0.933. The proposed saturation response calibration strategy exhibits good universality and practicability in biological detection applications, providing theoretical and experimental support for the transition of mass-manufactured nanosensors from theoretical research to practical application.

A hyper-distance-based method for hypernetwork comparison.

Hypernetwork is a useful way to depict multiple connections between nodes, making it an ideal tool for representing complex relationships in network science. In recent years, there has been a marked increase in studies on hypernetworks; however, the comparison of the difference between two hypernetworks has received less attention. This paper proposes a hyper-distance (HD)-based method for comparing hypernetworks. The method is based on higher-order information, i.e, the higher-order distance between nodes and Jensen-Shannon divergence. Experiments carried out on synthetic hypernetworks have shown that HD is capable of distinguishing between hypernetworks generated with different parameters, and it is successful in the classification of hypernetworks. Furthermore, HD outperforms current state-of-the-art baselines to distinguish empirical hypernetworks when hyperedges are randomly perturbed.

Synthesis and evaluation of 5,15-diaryltetrabenzoporphyrins as photosensitizers for photo-diagnosis and photodynamic activity of tumors.

Photodynamic therapy (PDT) is a well-established treatment modality, typically conducted with single-wavelength irradiation, which may not always be optimal for varying tumor locations and sizes. To address this, photosensitizers with absorption wavelengths ranging from 550 to 760 nm are being explored. Herein, a series of 5,15-diaryltetrabenzoporphyrins (Ar2TBPs) were synthesized. All compounds displayed obvious absorption at 550-700 nm (especially at ∼668 nm), intense fluorescence, efficient generation of singlet oxygen and good photodynamic antitumor effects. Notably, compound I3 (5,15-bis[(4-carboxymethoxy)phenyl]tetrabenzoporphyrin) showed excellent cytotoxicity against Eca-109 cell line upon red light irradiation, with an IC50 value of 0.45 µM, and phototherapeutic index of 25.8. Flow cytometry revealed that I3 could induce distinct cell apoptosis. In vivo studies revealed that compound I3 selectively accumulated at tumor site and exhibited outstanding PDT effect with antitumor activity under single-time administration and light irradiation, and revealed more efficiency than the clinical photosensitizer Verteporfin. These findings underscore the considerable promise of I3 as a robust theranostic agent, offering capabilities in real-time fluorescence imaging and serving as a potent photosensitizer for personalized and precise photodynamic therapy of tumors.

Transcriptomic Identification of Potential C2H2 Zinc Finger Protein Transcription Factors in Pinus massoniana in Response to Biotic and Abiotic Stresses.

Biotic and abiotic stresses have already seriously restricted the growth and development of Pinus massoniana, thereby influencing the quality and yield of its wood and turpentine. Recent studies have shown that C2H2 zinc finger protein transcription factors play an important role in biotic and abiotic stress response. However, the members and expression patterns of C2H2 TFs in response to stresses in P. massoniana have not been performed. In this paper, 57 C2H2 zinc finger proteins of P. massoniana were identified and divided into five subgroups according to a phylogenetic analysis. In addition, six Q-type PmC2H2-ZFPs containing the plant-specific motif 'QALGGH' were selected for further study under different stresses. The findings demonstrated that PmC2H2-ZFPs exhibit responsiveness towards various abiotic stresses, including drought, NaCl, ABA, PEG, H2O2, etc., as well as biotic stress caused by the pine wood nematode. In addition, PmC2H2-4 and PmC2H2-20 were nuclear localization proteins, and PmC2H2-20 was a transcriptional activator. PmC2H2-20 was selected as a potential transcriptional regulator in response to various stresses in P. massoniana. These findings laid a foundation for further study on the role of PmC2H2-ZFPs in stress tolerance.

The Serum NLRP1 Level and Coronary Artery Calcification: From Association to Development of a Risk-Prediction Nomogram.

Background: To investigate the correlation between inflammasomes and coronary artery calcification (CAC), and develop and validating a nomogram for predicting the risk of CAC in patients with coronary artery disease (CAD). Methods: A total of 626 patients with CAD at the Affiliated Hospital of Xuzhou Medical University were enrolled in this study. The patients were divided into the calcification group and the non-calcification group based on the assessment of coronary calcification. We constructed a training set and a validation set through random assignment. The least absolute shrinkage and selection operator (LASSO) regression and multivariate analysis were performed to identify independent risk factors of CAC in patients with CAD. Based on these independent predictors, we developed a web-based dynamic nomogram prediction model. The area under the receiver operating characteristic curve (AUC-ROC), calibration curves, and decision curve analysis (DCA) were used to evaluate this nomogram. Results: Age, smoking, diabetes mellitus (DM), hyperlipidemia, the serum level of nucleotide-binding oligomerization domain (NOD)-like receptor protein 1 (NLRP1), alkaline phosphatase (ALP) and triglycerides (TG) were identified as independent risk factors of CAC. The AUC-ROC of the nomogram is 0.881 (95% confidence interval (CI): 0.850-0.912) in the training set and 0.825 (95% CI: 0.760-0.876) in the validation set, implying high discriminative ability. Satisfactory performance of this model was confirmed using calibration curves and DCA. Conclusions: The serum NLRP1 level is an independent predictor of CAC. We established a web-based dynamic nomogram, providing a more accurate estimation and comprehensive perspective for predicting the risk of CAC in patients with CAD.

Directed differentiation of pancreatic δ cells from human pluripotent stem cells.

Dysfunction of pancreatic δ cells contributes to the etiology of diabetes. Despite their important role, human δ cells are scarce, limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. Here, we demonstrate that fibroblast growth factor (FGF) 7 promotes pancreatic endoderm/progenitor differentiation, whereas FGF2 biases cells towards the pancreatic δ-cell lineage via FGF receptor 1. We develop a differentiation method to generate δ cells from human stem cells by combining FGF2 with FGF7, which synergistically directs pancreatic lineage differentiation and modulates the expression of transcription factors and SST activators during endoderm/endocrine precursor induction. These δ cells display mature RNA profiles and fine secretory granules, secrete somatostatin in response to various stimuli, and suppress insulin secretion from in vitro co-cultured ß cells and mouse ß cells upon transplantation. The generation of human pancreatic δ cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation studies in diabetes.

Assessment of soft and hard tissue changes following micro crestal flap-Alveolar ridge preservation and augmentation at molar extraction sites in patients with stage III/IV periodontitis: A randomized controlled trial.

AIM: This study aimed to assess hard and soft tissue contour changes following micro crestal flap-alveolar ridge preservation (MCF-ARP) and natural healing (NH) in periodontally compromised molar extraction sites and to analyse the feasibility and need for bone augmentation during implant therapy. MATERIALS AND METHODS: Fifty-six patients with 70 sites were randomized into two groups at the site level (35 sites from 31 patients in the test group and 35 sites from 29 patients in the control group). Among whom, four patients contributed one tooth to the control group and one tooth to the test group. Hard tissue indicators were measured using cone beam computed tomography performed before tooth extraction and 6 months after surgery. Soft tissue contour changes were assessed using intraoral scanning performed before and immediately after surgery and also 2 weeks and 1, 3 and 6 months after surgery. RESULTS: Six months after surgery, the MCF-ARP group showed less resorption in buccal bone height (p = .032) and greater augmentation in central bone height (p = .001) and ridge width (p = .009). The mean, vertical and horizontal collapse of buccal soft tissue contour in the MCF-ARP group were 0.95 mm (p = .010), 0.61 mm (p = .019) and 0.56 mm (p = .013) less than that in the NH group, respectively. There were significantly (p = .007) fewer sites in the MCF-ARP group than in the NH group (0% vs. 26.7%) for staged bone augmentation and more sites that could be treated with simple implant procedure in the MCF-ARP group than in the NH group (71.9% vs. 56.6%). CONCLUSIONS: Compared with NH, MCF-ARP reduced bone resorption in periodontally compromised molar extraction sites and maintained the buccal soft tissue contour. MCF-ARP reduces the need for complex bone augmentation procedures in implant therapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on 4 February 2022, Version 1.0.

The benefit of favorable venous outflow profiles is mediated through the reduced risk of intracranial hemorrhage in acute ischemic stroke patients undergoing endovascular treatment.

BACKGROUND: Favorable venous outflow (VO) has been recognized as an independent predictor of excellent clinical outcomes in acute ischemic stroke caused by anterior circulation large vessel occlusion (AIS-LVO) patients who received endovascular treatment (EVT). However, the reasons why VO affects clinical outcomes have not been fully explained. In this study, we aimed to identify the potential mediators of VO affecting prognosis. METHODS: We conducted a multicenter retrospective cohort study of consecutive patients with AIS-LVO who underwent EVT. Baseline computed tomographic angiography (CTA) was applied to assess VO by the Cortical Vein Opacification Score (COVES). The primary outcome was functional independence at 90 days (modified Rankin Scale (mRS) score of 0-2). Classifying subtypes of intracranial hemorrhage (ICH) to explore the relationship between ICH subtypes and VO. Multivariate logistic regression and causal mediation analyses were used to evaluate the relationship among VO, functional independence, and potential mediators. RESULTS: Among 860 AIS-LVO patients undergoing EVT, a total of 515 patients were included in the present study after strict screening. In multivariate logistic regression analysis, favorable VO profiles (defined as COVES 3-6) were significantly associated with a lower incidence of ICH (24.2% vs 46.9%, adjusted odds ratio (aOR) 0.48, 95% confidence interval (CI) 0.30 to 0.77, P=0.002) and a higher proportion of functional independence (58.9% vs 15.0%, aOR 4.07, 95% CI 2.41 to 6.88, P<0.001). Mediation analysis showed that favorable VO profiles significantly reduced the incidence of parencuymal hematoma (PH) 2 accounting for 8.0% (95% CI 0.9% to 19.0%) of its beneficial effect on functional independence. CONCLUSION: This study demonstrated the potential mediating effects of severe ICH for the beneficial effect of favorable VO on clinical prognosis among patients with AIS-LVO who underwent EVT.