Exploring the impact of pre-anastomosis cerebral microcirculation on cerebral hyperperfusion syndrome in superficial temporal artery-middle cerebral artery bypass surgery of moyamoya disease.

Significance: Cerebral hyperperfusion syndrome (CHS), characterized by neurologic deficits due to postoperative high cerebral perfusion, is a serious complication of superficial temporal artery-middle cerebral artery (STA-MCA) surgery for moyamoya disease (MMD). Aim: We aim to clarify the importance of assessing pre-anastomosis cerebral microcirculation levels by linking the onset of CHS to pre- and post-anastomosis hemodynamics. Approach: Intraoperative laser speckle contrast imaging (LSCI) measured changes in regional cerebral blood flow (rCBF) and regional blood flow structuring (rBFS) within the cerebral cortical microcirculation of 48 adults with MMD. Results: Following anastomosis, all MMD patients exhibited a significant increase in rCBF ( 279.60 % ± 120.00 % , p < 0.001 ). Changes in rCBF and rBFS showed a negative correlation with their respective baseline levels (rCBF, p < 0.001 ; rBFS, p = 0.005 ). Baseline rCBF differed significantly between CHS and non-CHS groups ( p = 0.0049 ). The areas under the receiver operating characteristic (ROC) curve for baseline rCBF was 0.753. Hemorrhagic MMD patients showed higher baseline rCBF than ischemic patients ( p = 0.036 ), with a marked correlation between pre- and post-anastomosis rCBF in hemorrhagic cases ( p = 0.003 ), whereas ischemic MMD patients did not. Conclusion: Patients with low levels of pre-anastomosis baseline CBF induce a dramatic increase in post-anastomosis and show a high risk of postoperative CHS.

Morphology and Texture-Guided Deep Neural Network for Intracranial Aneurysm Segmentation in 3D TOF-MRA.

This study concentrates on the segmentation of intracranial aneurysms, a pivotal aspect of diagnosis and treatment planning. We aim to overcome the inherent instance imbalance and morphological variability by introducing a novel morphology and texture loss reweighting approach. Our innovative method involves the incorporation of tailored weights within the loss function of deep neural networks. Specifically designed to account for aneurysm size, shape, and texture, this approach strategically guides the model to focus on capturing discriminative information from imbalanced features. The study conducted extensive experimentation utilizing ADAM and RENJI TOF-MRA datasets to validate the proposed approach. The results of our experimentation demonstrate the remarkable effectiveness of the introduced methodology in improving aneurysm segmentation accuracy. By dynamically adapting to the variances present in aneurysm features, our model showcases promising outcomes for accurate diagnostic insights. The nuanced consideration of morphological and textural nuances within the loss function proves instrumental in overcoming the challenge posed by instance imbalance. In conclusion, our study presents a nuanced solution to the intricate challenge of intracranial aneurysm segmentation. The proposed morphology and texture loss reweighting approach, with its tailored weights and dynamic adaptability, proves to be instrumental in enhancing segmentation precision. The promising outcomes from our experimentation suggest the potential for accurate diagnostic insights and informed treatment strategies, marking a significant advancement in this critical domain of medical imaging.

Dual actions of chloroinconazide on pepper blight in Capsicum annuum: disruption of Phytophthora capsici mycelium and activation of CaCNGC9-mediated SA signaling.

BACKGROUND: Pepper blight, caused by Phytophthora capsici, is a devastating disease that seriously threatens pepper production worldwide. With the emergence of resistance in P. capsici against conventional fungicides, there is an urgent need to explore novel alternatives for pepper blight management. This study aims to assess the inhibitory effect of chloroinconazide (CHI), a compound synthesized from tryptophan, against pepper blight, and to explore its potential mechanisms of action. RESULTS: The results demonstrated that CHI effectively targeted P. capsici, disrupting its growth and mycelial structure, which resulted in the release of dissolved intracellular substances. Additionally, CHI significantly inhibited the sporangium formation, zoospores release, and zoospores germination, thereby reducing the re-infection of P. capsici. In contrast, the commercial pesticide methylaxyl only inhibited mycelial growth and had limited effect on re-infection, while azoxystrobin inhibited re-infection but had a weak inhibitory effect on mycelial growth. Furthermore, CHI activated the salicylic acid (SA) signaling pathway-mediated immune response to inhibit P. capsici infection in pepper, with this activation being contingent upon cyclic nucleotide-gated ion channel CaCNGC9. CONCLUSION: CHI exhibited potent dual inhibitory effects on P. capsici by disrupting mycelial structure and activating the CaCNGC9-mediated SA signaling pathway. These dual mechanisms of action suggested that CHI could serve as a promising alternative chemical fungicide for the effective management of pepper blight, offering a new approach to control this devastating disease. Our findings highlighted the potential of CHI as a sustainable and efficient solution to combat the increasing resistance of P. capsici to conventional fungicides, ensuring better crop protection and yield. © 2024 Society of Chemical Industry.

Potential role of endothelial progenitor cells in the pathogenesis and treatment of cerebral aneurysm.

Cerebral aneurysm (CA) is a significant health concern that results from pathological dilations of blood vessels in the brain and can lead to severe and potentially life-threatening conditions. While the pathogenesis of CA is complex, emerging studies suggest that endothelial progenitor cells (EPCs) play a crucial role. In this paper, we conducted a comprehensive literature review to investigate the potential role of EPCs in the pathogenesis and treatment of CA. Current research indicates that a decreased count and dysfunction of EPCs disrupt the balance between endothelial dysfunction and repair, thus increasing the risk of CA formation. Reversing these EPCs abnormalities may reduce the progression of vascular degeneration after aneurysm induction, indicating EPCs as a promising target for developing new therapeutic strategies to facilitate CA repair. This has motivated researchers to develop novel treatment options, including drug applications, endovascular-combined and tissue engineering therapies. Although preclinical studies have shown promising results, there is still a considerable way to go before clinical translation and eventual benefits for patients. Nonetheless, these findings offer hope for improving the treatment and management of this condition.

Customized T-time inner sampling network with uncertainty-aware data augmentation strategy for multi-annotated lesion segmentation.

Segmentation in medical images is inherently ambiguous. It is crucial to capture the uncertainty in lesion segmentations to assist cancer diagnosis and further interventions. Recent works have made great progress in generating multiple plausible segmentation results as diversified references to account for the uncertainty in lesion segmentations. However, the efficiency of existing models is limited, and the uncertainty information lying in multi-annotated datasets remains to be fully utilized. In this study, we propose a series of methods to corporately deal with the above limitation and leverage the abundant information in multi-annotated datasets: (1) Customized T-time Inner Sampling Network to promote the modeling flexibility and efficiently generate samples matching the ground-truth distribution of a number of annotators; (2) Uncertainty Degree defined for quantitatively measuring the uncertainty of each sample and the imbalance of the whole multi-annotated dataset from a brand new perspective; (3) Uncertainty-aware Data Augmentation Strategy to help probabilistic models adaptively fit samples with different ranges of uncertainty. We have evaluated each of them on both the publicly available lung nodule dataset and our in-house Liver Tumor dataset. Results show that our proposed methods achieves the overall best performance on both accuracy and efficiency, demonstrating its great potential in lesion segmentations and more downstream tasks in real clinical scenarios.

Quantifying irregular pulsation of intracranial aneurysms using 4D-CTA.

Recent studies have suggested that irregular pulsation of intracranial aneurysm during the cardiac cycle may be potentially associated with aneurysm rupture risk. However, there is a lack of quantification method for irregular pulsations. This study aims to quantify irregular pulsations by the displacement and strain distribution of the intracranial aneurysm surface during the cardiac cycle using four-dimensional CT angiographic image data. Four-dimensional CT angiography was performed in 8 patients. The image data of a cardiac cycle was divided into approximately 20 phases, and irregular pulsations were detected in four intracranial aneurysms by visual observation, and then the displacement and strain of the intracranial aneurysm was quantified using coherent point drift and finite element method. The displacement and strain were compared between aneurysms with irregular and normal pulsations in two different ways (total and stepwise). The stepwise first principal strain was significantly higher in aneurysms with irregular than normal pulsations (0.20±0.01 vs 0.16±0.02, p=0.033). It was found that the irregular pulsations in intracranial aneurysms usually occur during the consecutive ascending or descending phase of volume changes during the cardiac cycle. In addition, no statistically significant difference was found in the aneurysm volume changes over the cardiac cycle between the two groups. Our method can successfully quantify the displacement and strain changes in the intracranial aneurysm during the cardiac cycle, which may be proven to be a useful tool to quantify intracranial aneurysm deformability and aid in aneurysm rupture risk assessment.

Mindfulness-Based Interventions on Psychological Comorbidities in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, lifelong disease, so IBD patients are highly susceptible to negative emotions, such as anxiety and depression, resulting in a reduced quality of life. Mindfulness-based intervention (MBI) is widely used to reduce stress, anxiety and depression in people. Therefore, this study conducted a systematic review of mindfulness-based intervention training on anxiety, depression, and quality of life in patients with IBD through meta-analysis. METHODS: Search papers in PubMed, Web of Science, Cochrane Library, Google Scholar, CNKI, Wanfang, and Embase databases. The search time limit was from the establishment of the database to May 2023. Randomized controlled trial studies of the effect of mindfulness intervention training on patients with IBD were screened, the included results were integrated and analyzed, and ReviewManager 5.4 was used for meta-analysis. RESULTS: A total of 14 studies with a total of 1030 IBD patients were included. A total of 10 studies showed that the anxiety of patients in the mindfulness intervention group was significantly reduced by (standard mean difference (SMD) = -0.73, 95% confidence interval (CI): -1.01 to -0.45) compared to the control group. 8 studies showed that the intervention group significantly reduced patients' depression (SMD = -0.60, 95% CI: -0.78 to -0.42). 7 studies showed that the patient's quality of life improved after mindfulness intervention (SMD = 0.66, 95% CI: 0.45-0.87). CONCLUSION: Mindfulness-based intervention training can improve anxiety, depression, and quality of life in patients with inflammatory bowel disease in the short term, but the long-term effects need to be confirmed by more randomized controlled trials.

Fluorogenic Chemical Probe Strategy for Precise Tracking of Mitochondrial Polarity.

Mitochondrial polarity is a critical indicator of numerous pathological and biological processes; thus, the development of fluorescent probes capable of targeting mitochondria and visually monitoring its polarity is of great significance. In this study, fluorescent probes were designed with a N, N-dialkylamino rhodol scaffold as the fluorophore sensitive to polarity environments, in which the alkyl chain length was adjusted rationally to obtain distinct polarity recognition modes. By integrating mitochondria targeting groups, three fluorogenic chemical probes ROML-1, ROML-2, and ROML-3 have been obtained, featuring the capability to target mitochondria and monitor its polarity precisely, dynamically and visually. The probes displayed a distinctive response to the alterations in polarity. ROML-1 and ROML-2 followed a turn-on pattern while ROML-3 was ratiometric. It has been demonstrated that the hypersensitivity to polarity and ratio fluorescence property of ROML-3 was attributed to methyl groups rather than ethyl or butyl groups. The introduction of short methyl chains made the dihedral angle between the dialkylamino substituent and fluorophore of ROML-3 (spirocyclic form) rotatable and enlarged the energy gap between the ground state and excited state, which has been validated by the results of density functional theory (DFT) calculations. Furthermore, ROML-3 was used to monitor mitochondrial polarity via confocal microscopy imaging, which revealed that compared to healthy cells the polarity of mitochondria in cancer cells was enhanced; meanwhile, the polarity of mitochondria in senescent cells was higher in contrast with young cells. The present probe ROML-3 has been proven to be an efficient tool to monitor mitochondrial polarity dynamics, which demonstrated potential significance in biomedical research and disease diagnosis.

Insights into the regulatory role of epigenetics in moyamoya disease: Current advances and future prospectives.

Moyamoya disease (MMD) is a progressive steno-occlusive cerebrovascular disorder that predominantly affecting East Asian populations. The intricate interplay of distinct and overlapping mechanisms, including genetic associations such as the RNF213-p.R4810K variant, contributes to the steno-occlusive lesions and moyamoya vessels. However, genetic mutations alone do not fully elucidate the occurrence of MMD, suggesting a potential role for epigenetic factors. Accruing evidence has unveiled the regulatory role of epigenetic markers, including DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), in regulating pivotal cellular and molecular processes implicated in the pathogenesis of MMD by modulating endothelial cells and smooth muscle cells. The profile of these epigenetic markers in cerebral vasculatures and circulation has been determined to identify potential diagnostic biomarkers and therapeutic targets. Furthermore, in vitro studies have demonstrated the multifaceted effects of modulating specific epigenetic markers on MMD pathogenesis. These findings hold great potential for the discovery of novel therapeutic targets, translational studies, and clinical applications. In this review, we comprehensively summarize the current understanding of epigenetic mechanisms, including DNA methylation, histone modifications, and ncRNAs, in the context of MMD. Furthermore, we discuss the potential challenges and opportunities that lie ahead in this rapidly evolving field.

Genome-Wide Transcriptome Analysis of a Virulent sRNA, Trans217, in Xanthomonas oryzae pv. oryzae (Xoo), the Causative Agent of Rice Bacterial Blight.

Small non-coding RNAs (sRNAs) act as post-transcriptional regulators to participate in many cellular processes. Among these, sRNA trans217 has been identified as a key virulent factor associated with pathogenicity in rice, triggering hypersensitive reactions in non-host tobacco and facilitating the secretion of the PthXo1 effector in Xanthomonas oryzae pv. oryzae (Xoo) strain PXO99A. Elucidating potential targets and downstream regulatory genes is crucial for understanding cellular networks governing pathogenicity and plant resistance. To explore the targets regulated by sRNA trans217, transcriptome sequencing was carried out to assess differential expression genes (DEGs) between the wild-type strain PXO99A and a mutant lacking the sRNA fragment under both virulence-inducing or normal growth conditions. DEG analysis revealed that sRNA trans217 was responsible for diverse functions, such as type III secretion system (T3SS), glutamate synthase activity, and oxidative stress response. Three genes were selected for further investigation due to their significant differential expression and biological relevance. Deletion of PXO_RS08490 attenuated the pathogenicity of Xoo in rice and reduced the tolerance level of PXO99A to hydrogen peroxide. These findings suggest a regulatory role of sRNA trans217 in modulating bacterial virulence through multiple gene targets, either directly or indirectly.

Identifying hemodynamic factors associated with the rupture of anterior communicating artery aneurysms based on global modeling of blood flow in the cerebral artery network.

Anterior communicating artery (ACoA) aneurysms are more prone to rupture compared to aneurysms present in other cerebral arteries. We hypothesize that systemic blood flow in the cerebral artery network plays an important role in shaping intra-aneurysmal hemodynamic environment thereby affecting the rupture risk of ACoA aneurysms. The majority of existing numerical studies in this field employed local modeling methods where the physical boundaries of a model are confined to the aneurysm region, which, though having the benefit of reducing computational cost, may compromise the physiological fidelity of numerical results due to insufficient account of systemic cerebral arterial hemodynamics. In the present study, we firstly carried out numerical experiments to address the difference between the outcomes of local and global modeling methods, demonstrating that local modeling confined to the aneurysm region results in inaccurate predictions of hemodynamic parameters compared with global modeling of the ACoA aneurysm as part of the cerebral artery network. Motivated by this finding, we built global hemodynamic models for 40 ACoA aneurysms (including 20 ruptured and 20 unruptured ones) based on medical image data. Statistical analysis of the computed hemodynamic data revealed that maximum wall shear stress (WSS), minimum WSS divergence, and maximum WSS gradient differed significantly between the ruptured and unruptured ACoA aneurysms. Optimal threshold values of high/low WSS metrics were determined through a series of statistical tests. In the meantime, some morphological parameters of aneurysms, such as large nonsphericity index, aspect ratio, and bottleneck factor, were found to be associated closely with aneurysm rupture. Furthermore, multivariate logistic regression analyses were performed to derive models combining hemodynamic and morphological parameters for discriminating the rupture status of aneurysms. The capability of the models in rupture status discrimination was high, with the area under the receiver operating characteristic curve reaching up to 0.9. The findings of the study suggest that global modeling of the cerebral artery network is essential for reliable quantification of hemodynamics in ACoA aneurysms, disturbed WSS and irregular aneurysm morphology are associated closely with aneurysm rupture, and multivariate models integrating hemodynamic and morphological parameters have high potential for assessing the rupture risk of ACoA aneurysms.

Optimizing timing for quantification of intracranial aneurysm enhancement: a multi-phase contrast-enhanced vessel wall MRI study.

OBJECTIVES: Aneurysm wall enhancement (AWE) on high-resolution contrast-enhanced vessel wall MRI (VWMRI) is an emerging biomarker for intracranial aneurysms (IAs) stability. Quantification methods of AWE in the literature, however, are variable. We aimed to determine the optimal post-contrast timing to quantify AWE in both saccular and fusiform IAs. MATERIALS AND METHODS: Consecutive patients with unruptured IAs were prospectively recruited. VWMRI was acquired on 1 pre-contrast and 4 consecutive post-contrast phases (each phase was 9 min). Signal intensity values of cerebrospinal fluid (CSF) and aneurysm wall on pre- and 4 post-contrast phases were measured to determine the aneurysm wall enhancement index (WEI). AWE was also qualitatively analyzed on post-contrast images using previous grading criteria. The dynamic changes of AWE grade and WEI were analyzed for both saccular and fusiform IAs. RESULTS: Thirty-four patients with 42 IAs (27 saccular IAs and 15 fusiform IAs) were included. The changes in AWE grade occurred in 8 (30%) saccular IAs and 6 (40%) in fusiform IAs during the 4 post-contrast phases. The WEI of fusiform IAs decreased 22.0% over time after contrast enhancement (p = 0.009), while the WEI of saccular IAs kept constant during the 4 post-contrast phases (p > 0.05). CONCLUSIONS: When performing quantitative analysis of AWE, acquiring post-contrast VWMRI immediately after contrast injection achieves the strongest AWE for fusiform IAs. While the AWE degree is stable for 36 min after contrast injection for saccular IAs. CLINICAL RELEVANCE STATEMENT: The standardization of imaging protocols and analysis methods for AWE will be helpful for imaging surveillance and further treatment decisions of patients with unruptured IAs. KEY POINTS: Imaging protocols and measurements of intracranial aneurysm wall enhancement are reported heterogeneously. Aneurysm wall enhancement for fusiform intracranial aneurysms (IAs) is strongest immediately post-contrast, and stable for 36 min for saccular IAs. Future multi-center studies should investigate aneurysm wall enhancement as an emerging marker of aneurysm growth and rupture.

Rictor/mTORC2 signalling contributes to renal vascular endothelial-to-mesenchymal transition and renal allograft interstitial fibrosis by regulating BNIP3-mediated mitophagy.

BACKGROUND: Renal allograft interstitial fibrosis/tubular atrophy (IF/TA) constitutes the principal histopathological characteristic of chronic allograft dysfunction (CAD) in kidney-transplanted patients. While renal vascular endothelial-mesenchymal transition (EndMT) has been verified as an important contributing factor to IF/TA in CAD patients, its underlying mechanisms remain obscure. Through single-cell transcriptomic analysis, we identified Rictor as a potential pivotal mediator for EndMT. This investigation sought to elucidate the role of Rictor/mTORC2 signalling in the pathogenesis of renal allograft interstitial fibrosis and the associated mechanisms. METHODS: The influence of the Rictor/mTOR2 pathway on renal vascular EndMT and renal allograft fibrosis was investigated by cell experiments and Rictor depletion in renal allogeneic transplantation mice models. Subsequently, a series of assays were conducted to explore the underlying mechanisms of the enhanced mitophagy and the ameliorated EndMT resulting from Rictor knockout. RESULTS: Our findings revealed a significant activation of the Rictor/mTORC2 signalling in CAD patients and allogeneic kidney transplanted mice. The suppression of Rictor/mTORC2 signalling alleviated TNFα-induced EndMT in HUVECs. Moreover, Rictor knockout in endothelial cells remarkably ameliorated renal vascular EndMT and allograft interstitial fibrosis in allogeneic kidney transplanted mice. Mechanistically, Rictor knockout resulted in an augmented BNIP3-mediated mitophagy in endothelial cells. Furthermore, Rictor/mTORC2 facilitated the MARCH5-mediated degradation of BNIP3 at the K130 site through K48-linked ubiquitination, thereby regulating mitophagy activity. Subsequent experiments also demonstrated that BNIP3 knockdown nearly reversed the enhanced mitophagy and mitigated EndMT and allograft interstitial fibrosis induced by Rictor knockout. CONCLUSIONS: Consequently, our study underscores Rictor/mTORC2 signalling as a critical mediator of renal vascular EndMT and allograft interstitial fibrosis progression, exerting its impact through regulating BNIP3-mediated mitophagy. This insight unveils a potential therapeutic target for mitigating renal allograft interstitial fibrosis.

Liquid chromatography coupled to mass spectrometry metabolomic analysis of cerebrospinal fluid revealed the metabolic characteristics of moyamoya disease.

Objective: Metabolomics has found extensive applications in the field of neurological diseases, significantly contributing to their diagnosis and treatment. However, there has been limited research applying metabolomics to moyamoya disease (MMD). This study aims to investigate and identify differential metabolites associated with MMD. Methods: We employed a liquid chromatography coupled with mass spectrometry (LC-MS) approach, complemented by univariate and multivariate analyses, to discern metabolic biomarkers in cerebrospinal fluid samples. We then compared these biomarkers between MMD patients and healthy controls (Ctl). Results: Sixteen patients diagnosed with MMD via cerebral angiography and eight healthy controls were enrolled in this study. Comparative analyses, including univariate and multivariate analyses, correlation studies, heatmaps, Volcano Plots, and KEGG pathway enrichment, were performed between MMD patients and controls. As a result, we identified 129 significant differential metabolites in the cerebrospinal fluid between MMD patients and controls. These metabolic biomarkers are associated with various pathways, with notable involvement in purine and pyrimidine metabolism. Conclusion: Utilizing an LC-MS-based metabolomics approach holds promise for enhancing the clinical diagnosis of MMD. The identified biomarkers offer potential avenues for the development of novel diagnostic methods for MMD and offer fresh insights into the pathogenesis of the disease.

Development and Validation of an ADA-Tolerant Assay for Quantification of an Exatecan-Based ADC in Monkey Plasma.

BACKGROUND: The development of an anti-drug antibody (ADA)-tolerant pharmacokinetic (PK) assay is important when the drug exposure is irrelevant to toxicity in the presence of ADA. We aimed to develop and validate an ADA-tolerant assay for an exatecan-based antibody-drug conjugate (ADC) in monkey plasma. RESULTS: The assay tolerated 5.00 µg/mL of ADA at 12 µg/mL of ADC. Its accuracy and precision results satisfied the acceptance criteria. Furthermore, the assay was free from hook and matrix effects and exhibited good dilutional linearity. Additionally, the ADC in plasma samples was stable under different storage conditions. METHOD: An ADA-tolerant ADC assay was configured with an anti-payload antibody for capture, and a drug-target protein combined with a horseradish peroxidase (HRP)-labeled antibody against a drug-target-protein tag for detection. Samples were firstly acidified to dissociate drug and ADA complexes, and to convert the carboxylate form to the lactone form of exatecan molecules; then, the ADAs in the samples were removed with a naked antibody-coated microplate. The treated samples were further incubated with coated anti-payload antibody and captured ADC molecules were quantified by the detection reagent. The developed assay was optimized and validated against regulatory guidelines. CONCLUSIONS: The assay met both methodological and sample-related ADA tolerance requirements, and was applicable to a nonclinical study in cynomolgus monkeys.

Delayed Enhancement of Intracranial Atherosclerotic Plaque Can Better Differentiate Culprit Lesions: A Multiphase Contrast-Enhanced Vessel Wall MRI Study.

BACKGROUND AND PURPOSE: Intracranial plaque enhancement (IPE) identified by contrast-enhanced vessel wall MR imaging (VW-MR imaging) is an emerging marker of plaque instability related to stroke risk, but there was no standardized timing for postcontrast acquisition. We aim to explore the optimal postcontrast timing by using multiphase contrast-enhanced VW-MR imaging and to test its performance in differentiating culprit and nonculprit lesions. MATERIALS AND METHODS: Patients with acute ischemic stroke due to intracranial plaque were prospectively recruited to undergo VW-MR imaging with 1 precontrast phase and 4 consecutive postcontrast phases (9 minutes and 13 seconds for each phase). The signal intensity (SI) values of the CSF and intracranial plaque were measured on 1 precontrast and 4 postcontrast phases to determine the intracranial plaque enhancement index (PEI). The dynamic changes of the PEI were compared between culprit and nonculprit plaques on the postcontrast acquisitions. RESULTS: Thirty patients with acute stroke (aged 59 ± 10 years, 18 [60%] men) with 113 intracranial plaques were included. The average PEI of all intracranial plaques significantly increased (up to 14%) over the 4 phases. There was significantly increased PEI over the 4 phases for culprit plaques (an average increase of 23%), but this was not observed for nonculprit plaques. For differentiating culprit and nonculprit plaques, we observed that the performance of IPE in the second postcontrast phase (cutoff = 0.83, AUC = 0.829 [0.746-0.893]) exhibited superior accuracy when compared with PEI in the first postcontrast phase (cutoff = 0.48; AUC = 0.768 [0.680-0.843]) (P = .022). CONCLUSIONS: A 9-minute delay of postcontrast acquisition can maximize plaque enhancement and better differentiate between culprit and nonculprit plaques. In addition, culprit and nonculprit plaques have different enhancement temporal patterns, which should be evaluated in future studies.

NSD2 modulates Drp1-mediated mitochondrial fission in chronic renal allograft interstitial fibrosis by methylating STAT1.

Renal interstitial fibrosis/tubular atrophy (IF/TA) is a prominent pathological feature of chronic allograft dysfunction (CAD). Our previous study has demonstrated that epithelial-mesenchymal transition (EMT) plays a significant role in shaping the development of IF/TA. Nuclear SET domain (NSD2), a histone methyltransferase catalyzing methylation at lysine 36 of histone 3, is crucially involved in the development and progression of solid tumors. But its role in the development of renal allograft interstitial fibrosis has yet to be elucidated. Here, we characterize NSD2 as a crucial mediator in the mouse renal transplantation model in vivo and a model of tumor necrosis factor-α (TNF-α) stimulated-human renal tubular epithelial cells (HK-2) in vitro. Functionally, NSD2 knockdown inhibits EMT, dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in mice. Conversely, NSD2 overexpression exacerbates fibrosis-associated phenotypes and mitochondrial fission in tubular cells. Mechanistically, tubular NSD2 aggravated the Drp-1 mediated mitochondrial fission via STAT1/ERK/PI3K/Akt signaling pathway in TNF-α-induced epithelial cell models. Momentously, mass spectrometry (MS) Analysis and site-directed mutagenesis assays revealed that NSD2 interacted with and induced Mono-methylation of STAT1 on K173, leading to its phosphorylation, IMB1-dependent nuclear translocation and subsequent influence on TNF-α-induced EMT and mitochondrial fission in NSD2-dependent manner. Collectively, these findings shed light on the mechanisms and suggest that targeting NSD2 could be a promising therapeutic approach to enhance tubular cell survival and alleviate interstitial fibrosis in renal allografts during CAD.

Intraoperative evaluation of local cerebral hemodynamic change by laser speckle contrast imaging for predicting postoperative cerebral hyperperfusion during STA-MCA bypass in adult patients with moyamoya disease.

Cerebral hyperperfusion (CHP) occurred frequently after direct superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery for moyamoya disease (MMD). We analyzed cortical microvascular density (CMD) and the change of cerebral blood flow (LΔCBF) using intraoperative laser speckle contrast imaging (LSCI) on 130 hemispheres of 95 consecutive adult patients with MMD. The demographic characteristics, cortical hemodynamic sources, bypass methods, intraoperative blood flow data, and relative CBF changes on single-photon emission computed tomography (SPECT) examination (SΔrCBF) were compared between the groups with and without CHP. The median values for CMD, LΔCBF, and SΔrCBF were significantly higher in the CHP group than in the non-CHP group (CMD 0.240 vs 0.206, P = 0.004; LΔCBF 2.285 vs 1.870, P < 0.001; SΔCBF 1.535 vs 1.260, P < 0.001). Multivariate analysis revealed that hemodynamic sources of recipient parasylvian cortical arteries from MCA (M-PSCAs), end-to-side (E-S) bypass method, CMD ≥ 0.217, and LΔCBF ≥ 1.985 were the risk factors for CHP. Intraoperative LSCI was useful for evaluating hemodynamics and predicting CHP in patients with MMD.

Associations between atherosclerotic luminal stenosis in the distal internal carotid artery and diffuse wall thickening in its upstream segment.

OBJECTIVES: Significant atherosclerotic stenosis or occlusion in the distal internal carotid artery (ICA) may induce diffuse wall thickening (DWT) in the upstream arterial wall. This study aimed to assess the association of atherosclerotic steno-occlusive diseases in the distal ICA with DWT in the upstream ipsilateral ICA. METHODS: Individuals with atherosclerotic stenosis in the distal ICA, detected by carotid MR vessel wall imaging using 3D pre- and post-contrast T1 volume isotropic turbo spin-echo acquisition (T1-VISTA) sequence, were enrolled. The associations of vessel wall thickening, the longitudinal extent of DWT, enhancement of the upstream ipsilateral ICA, and stenosis degree in the distal ICA were examined. RESULTS: Totally 64 arteries in 55 patients with atherosclerotic steno-occlusive distal ICAs were included. Significant correlations were found between distal ICA stenosis and DWT in the petrous ICA (r = 0.422, p = 0.001), DWT severity (r = 0.474, p < 0.001), the longitudinal extent of DWT in the ICA (r = 0.671, p < 0.001), enhancement in the petrous ICA (r = 0.409, p = 0.001), and enhancement degree (r = 0.651, p < 0.001). In addition, high degree of enhancement was correlated with both increased wall thickness and increased prevalence of DWT in the petrous ICA (both p < 0.001). CONCLUSIONS: DWT of the petrous ICA is commonly detected in patients with atherosclerotic steno-occlusive disease in the distal ICA. The degree of stenosis in the distal ICA is associated with wall thickening and its longitudinal extent in the upstream segments. CLINICAL RELEVANCE STATEMENT: Diffuse wall thickening is a common secondary change in atherosclerotic steno-occlusive disease in the intracranial carotid. This phenomenon constitutes a confounding factor in the distinction between atherosclerosis and inflammatory vasculopathies, and could be reversed after alleviated atherosclerotic stenosis. KEY POINTS: • Diffuse wall thickening of the petrous internal carotid artery is commonly detected in patients with atherosclerotic steno-occlusive disease in the distal internal carotid artery. • The phenomenon of diffuse wall thickening could be reversed after stenosis alleviation. • Carotid artery atherosclerosis with diffuse wall thickening should warrant a differential diagnosis from other steno-occlusive diseases, including moyamoya diseases and Takayasu aortitis.