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Background and purposeIndividuals with intracranial artery occlusion have high rates of ischaemic events and recurrence. It has been challenging to identify patients who had high-risk stroke using a simple, valid and non-invasive screening approach. This study aimed to investigate whether fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH), a specific imaging sign on the FLAIR sequence, could be a predictor of ischaemic events in a population with internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion.MethodsWe retrospectively analysed 147 patients (mean 60.43±12.83 years) with 149 lesions, including 37 asymptomatic and 112 symptomatic cases of ICA or MCA occlusion. Symptomatic occlusion was considered if ischaemic events were present in the relevant territory within 90 days. FVH Alberta Stroke Program Early Computed Tomography Score (FVH-ASPECTS: 0–7, with 0 indicating absence of FVH and 7 suggesting prominent FVH) and collateral circulation grade were assessed for each participant. Multivariable logistic regression analysis was performed to detect independent markers associated with symptomatic status.ResultsA lower FVH-ASPECTS was associated with a more favourable collateral circulation grade (rho=−0.464, p<0.0001). The FVH-ASPECTS was significantly lower in the asymptomatic occlusion group than in the symptomatic occlusion group (p<0.0001). FVH-ASPECTS (Odd ratio, 2.973; 95% confidence interval, 1.849 to 4.781; p<0.0001) was independently associated with symptomatic status after adjustment for age, sex, lesion location and collateral circulation grade in the multivariate logistic regression. The area under the curve was 0.861 for the use of FVH-ASPECTS to identify symptomatic occlusion.ConclusionsThe ability to discriminate symptomatic from asymptomatic occlusion suggests that FVH may be a predictor of stroke. As a simple imaging sign, FVH may serve as a surrogate for haemodynamic impairments and can be used to identify high-risk stroke cases early in ICA or MCA occlusion.

Objectives We aim to investigate whether cerebral small vessel disease (cSVD) imaging markers correlate with deep medullary vein (DMV) damage in small vessel occlusion acute ischemic stroke (SVO-AIS) patients. Methods The DMV was divided into six segments according to the regional anatomy. The total DMV score (0–18) was calculated based on segmental continuity and visibility. The damage of DMV was grouped according to the quartiles of the total DMV score. Neuroimaging biomarkers of cSVD including white matter hyperintensity (WMH), cerebral microbleed (CMB), perivascular space (PVS), and lacune were identified. The cSVD score were further analyzed. Results We included 229 SVO-AIS patients, the mean age was 63.7 ± 23.1 years, the median NIHSS score was 3 (IQR, 2–6). In the severe DMV burden group (the 4th quartile), the NIHSS score grade (6 (3–9)) was significantly higher than other groups ( p  < 0.01). The grade scores for basal ganglia PVS (BG-PVS) were positively correlated with the degree of DMV ( R  = 0.67, p  < 0.01), rather than centrum semivole PVS (CS-PVS) ( R  = 0.17, p  = 0.1). In multivariate analysis, high CMB burden (adjusted odds ratio [aOR], 25.38; 95% confidence interval [CI], 1.87–345.23) was associated with severe DMV scores. In addition, BG-PVS was related to severe DMV burden in a dose-dependent manner: when BG-PVS score was 3 and 4, the aORs of severe DMV burden were 18.5 and 12.19, respectively. Conclusion The DMV impairment was associated with the severity of cSVD, which suggests that DMV burden may be used for risk stratification in SVO-AIS patients. Clinical relevance statement The DMV damage score, based on the association between small vessel disease and the deep medullary veins impairment, is a potential new imaging biomarker for the prognosis of small vessel occlusion acute ischemic stroke, with clinical management implications. Key Points • The damage to the deep medullary vein may be one mechanism of cerebral small vessel disease. • Severe burden of the basal ganglia perivascular space and cerebral microbleed is closely associated with significant impairment to the deep medullary vein. • The deep medullary vein damage score may reflect a risk of added vascular damage in small vessel occlusion acute ischemic stroke patients.

To explore the applicability of CT perfusion-derived parameters and collateral index in prediction of functional and clinical outcomes in patients with Moyamoya disease (MMD) who have not been treated surgically. All hemispheres were categorized into four groups: those with ischemic (IS) lesions, hemorrhagic (HE) lesions, subarachnoid hemorrhage (SAH) and normal hemisphere (NH). The clinical review included primary outcomes (whether a patient survived the cerebrovascular event) and secondary outcomes (the modified Rankin scale [mRS] and Katz-activity of daily living [ADL] scale). CTP-derived parameters of the frontal, temporal lobe and basal ganglia were calculated. Collateral index of the hypointensity ratio (HIR) was defined as a volume of Tmax >10 s/ Tmax >4 s. Between December 2020 and December 2021, 21 MMD patients (15 bilateral cases and 6 unilateral cases, for a total of 36 hemispheres) were retrospectively included. Compared with the NH group, the IS group showed obviously abnormal hemodynamics. As for the primary outcomes, HIR showed an excellent area under the curve of 0.955 (95 % CI: 0.886–1.000, p < 0.001). Significant correlations were found between CTP-derived parameters and secondary outcomes. Furthermore, HIR was significantly correlated with mRS (r = 0.576, p = 0.001) and ADL scores (r = 0.644, p < 0.001). Among different imaging types, IS hemispheres were characterized by distinct changes of hemodynamic parameters. Collateral index of HIR could be considered a clinically accessible and promising indictor of functional and clinical outcomes in MMD. •Ischemic MMD showed distinct perfusion abnormalities.•Collateral index of hypointensity ratio could predict survival or death after cerebrovascular events in MMD.•Collateral index of hypointensity ratio was correlated with mRS score and activity of daily living score.

Aims Our purpose is to assess the role of cerebral small vessel disease (SVD) in prediction models in patients with different subtypes of acute ischemic stroke (AIS). Methods We enrolled 398 small‐vessel occlusion (SVO) and 175 large artery atherosclerosis (LAA) AIS patients. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. MRI was performed to assess white matter hyperintensity (WMH), perivascular space (PVS), lacune, and cerebral microbleed (CMB). Logistic regression (LR) and machine learning (ML) were used to develop predictive models to assess the influences of SVD on the prognosis. Results In the feature evaluation of SVO‐AIS for different outcomes, the modified total SVD score (Gain: 0.38, 0.28) has the maximum weight, and periventricular WMH (Gain: 0.07, 0.09) was more important than deep WMH (Gain: 0.01, 0.01) in prognosis. In SVO‐AIS, SVD performed better than regular clinical data, which is the opposite of LAA‐AIS. Among all models, eXtreme gradient boosting (XGBoost) method with optimal index (OI) has the best performance to predict excellent outcome in SVO‐AIS. [0.91 (0.84–0.97)]. Conclusions Our results revealed that different SVD markers had distinct prognostic weights in AIS patients, and SVD burden alone may accurately predict the SVO‐AIS patients' prognosis. Characteristics of cerebral small vessel disease (CSVD) in acute ischemic stroke (AIS) patients can affect outcomes at 90 days. Meanwhile, different imaging markers of CSVD have different weights of impact on large artery atherosclerosis and small vessel occlusion subtype AIS.

The interaction effect between collateral circulation and ischemic core size on stroke outcomes has been highlighted in acute ischemic stroke (AIS). However, biomarkers that assess the magnitude of this interaction are still lacking. We aimed to present a new imaging marker, the collateral-core ratio (CCR), to quantify the interaction effect between these factors and evaluate its ability to predict functional outcomes using machine learning (ML) in AIS. Patients with AIS caused by anterior circulation large vessel occlusion (LVO) were recruited from a prospective multicenter study. CCR was calculated as collateral perfusion volume/ischemic core volume. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. An ML model was built and tested with a tenfold cross-validation using nine clinical and four imaging variables with mRS score 3–6 as unfavorable outcomes. Among 129 patients, CCR was identified as the most important variable. The prediction model incorporating clinical factors, ischemic core volume, collateral perfusion volume, and CCR showed better discriminatory power in predicting unfavorable outcomes than the model without CCR (mean C index 0.853 ± 0.108 versus 0.793 ± 0.133, P  = 0.70; mean net reclassification index 52.7% ± 32.7%, P  < 0.05). When patients were divided into two groups based on their CCR value with a threshold of 0.73, unfavorable outcomes were significantly more prevalent in patients with CCR ≤ 0.73 than in those with CCR > 0.73. CCR is a robust predictor of functional outcomes, as identified by ML, in patients with acute LVO. The prediction model that incorporated CCR improved the model’s ability to identify unfavorable outcomes. ClinicalTrials.gov Identifier: NCT02580097.

Background Breast cancer progression reflects heterogeneous malignant states shaped by clonal evolution and microenvironmental selection, yet how genomic instability quantitatively couples to transcriptional state transitions and spatial niche organization remains unclear. Methods We integrated single-cell RNA sequencing and spatial transcriptomics across ER-positive, HER2-positive, and triple-negative tumors, combined with CNV inference, branched trajectory analysis, transcription factor regulon modeling, cell–cell communication inference, and spatial niche mapping. Trajectory-derived evolutionary gene programs were translated to bulk-tumor stratification and multicohort prognostic modeling. MFGE8 was further evaluated as a therapeutic target using structure-based virtual screening with docking and molecular dynamics refinement. Functional validation of MFGE8 was performed using knockdown, overexpression, rescue, and in vitro phenotypic assays. Results Malignant epithelial cells formed a branched three-state trajectory that was strongly coupled to CNV-defined clonal architecture, with the tightest coupling in triple-negative tumors. Regulon analyses revealed coordinated transcription factor rewiring along progression, converging on a late State 3 program enriched for extracellular matrix and adhesion signaling. Spatial transcriptomics localized State 3 to a discrete invasive-front niche characterized by stromal-dominant ligand–receptor interactions. MFGE8 emerged as a State 3–biased output associated with LHX2 activity, and in silico MFGE8 perturbation induced transcriptional rollback from the late-state branch. Structure-guided screening prioritized candidate MFGE8 binders with stable interaction dynamics. Evolutionary gene programs enabled robust bulk stratification and supported a multicohort-validated 10-gene prognostic model associated with genomic instability patterns and immunotherapy-related signatures. Conclusions CNV-linked clonal evolution and spatial niche restriction are associated with a late malignant program and prioritize MFGE8 as a candidate late-state-associated therapeutic target in breast cancer.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, with liver metastasis representing the principal cause of death in CRC patients. Current primary treatment options for colorectal cancer liver metastases (CRLM) encompass chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, the survival rate for CRLM patients remains below 40%. The unique immune−tolerant microenvironment of the liver has recently been recognized as a central driver of metastatic colonization, immune evasion, and therapeutic resistance. This review examines the development of CRLM, with particular emphasis on recent therapeutic advances. It also explores promising research and emerging treatment strategies. A deeper understanding of CRLM pathogenesis and therapeutic progress will enable clinicians to optimize treatment approaches and improve patient outcomes.

Magnetic graphene oxide (MGO) is an inorganic composite material composed of graphene oxide (GO) that has the characteristics of GO and magnetic material. The application of MGO in water treatment can effectively solve problems such as difficult recovery of the adsorbed GO from liquid, low efficiency, and high treatment cost, which are regarded as having important academic research value. In this study, the properties, synthesis approaches, and characterization methods of MGO, as well as its adsorption effect and the mechanism of this composite material as an adsorbent of heavy metals, organic dyes, and rare earth ions during water treatment, are comprehensively summarized. Finally, the future development of MGO as a high-efficiency adsorbent is discussed to provide references regarding application of MGO in the field of water treatment.

BackgroundInherent limitations of single cancer therapy are overcome by multi-therapy modality, which integrates characteristics of each therapeutic modality and material chemistry. The multi-modal method has the potential for becoming one of the next generation options for cancer treatments. Photothermal therapy (PTT) is an efficient, non-invasive treatment method that can be used on various cancer types. We propose an acid-triggered self-destructing nano-biocatalyst integrated starvation/chemical/photothermal triple therapy that is based on design principles and biomedical applications of GOx cancer treatment methods.MethodsScanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potentials were used to analyze the physical as well as chemical properties of MoS2@DOX/GOx@MnO2 (M@D/G@M). Further, Fourier transform infra-red (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) were used to assess the compositions of the nanocatalysts. The biological effects of M@D/G@M on cells were studied in vitro by inverted fluorescence microscopy, confocal laser scanning microscopy (CLSM), flow cytometry, CCK-8 test, and hemolysis test. Treatment effects of the nanocatalysts were evaluated in MHCC-97H tumor BALB/c mice, whose body weights, tumor local temperature, tumor volumes, and tumor histological changes were evaluated.ResultsThere was a high DOX encapsulation efficiency of M@D/G@M (90.233%). The photothermal conversion efficiency (η) of M@D/G@M is 25.2%, and its oxygen production within 5 min reached 27.5 mg L−1. Cell internalization analysis showed that within 4 h, M@D/G@M was almost completely absorbed by HepG2 cells. Further, the highest red fluorescence and apoptosis effects of dead cells (59.07% apoptosis) as well as the lowest tumor volume index of mice (0.2862%) were observed in the M@D/G@M + pH6.0 + NIR treatment group.ConclusionsOur findings inform the development and applications of multi-modal methods in tumor therapy.

Chromosome copy number variations are poorly understood drivers of human malignancies. -7/del(7q) is common in acute myeloid leukemia, confers a poor prognosis, and is thought to harbor several tumor suppressors. Previously, we identified the histone methyltransferase KMT2C as a tumor suppressor in this region. Here, through a differentiation CRISPR screen in hematopoietic stem and progenitor cells, we find that the mitochondrial iron transporter ABCB8 is essential for their differentiation. ABCB8 deficiency accelerates leukemogenesis in vivo and disrupts iron homeostasis, reducing cytoplasmic iron availability and impairing iron-dependent enzymes, including the histone demethylase KDM6A. Consequently, ABCB8 loss elevates H3K27me3 levels, repressing differentiation genes in an iron- and KDM6A-dependent manner. Notably, ABCB8 and KMT2C, neighboring genes on 7q, cooperatively regulate H3K27me3 to suppress leukemogenesis. Our findings reveal ABCB8 as a tumor suppressor in -7/del(7q) acute myeloid leukemia and uncover an epigenetic collaboration between neighboring tumor suppressors, driven by iron-mediated chromatin remodeling.