IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation.

Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that the RNA helicase DDX5 was downregulated in keratinocytes from the inflammatory skin lesions in patients with atopic dermatitis and psoriasis, and that mice with keratinocyte-specific deletion of Ddx5 (Ddx5∆KC) were more susceptible to cutaneous inflammation. Inhibition of DDX5 expression in keratinocytes was induced by the cytokine interleukin (IL)-17D through activation of the CD93-p38 MAPK-AKT-SMAD2/3 signaling pathway and led to pre-messenger RNA splicing events that favored the production of membrane-bound, intact IL-36 receptor (IL-36R) at the expense of soluble IL-36R (sIL-36R) and to the selective amplification of IL-36R-mediated inflammatory responses and cutaneous inflammation. Restoration of sIL-36R in Ddx5∆KC mice with experimental atopic dermatitis or psoriasis suppressed skin inflammation and alleviated the disease phenotypes. These findings indicate that IL-17D modulation of DDX5 expression controls inflammation in keratinocytes during inflammatory skin diseases.

Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury.

BACKGROUND: Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play a major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis is a pro-inflammatory form of programmed cell death that has emerged as a new area of research in stroke. Nevertheless, the potential role of LCN2 in astrocyte pyroptosis remains unclear. METHODS: An ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in vivo. In this study, in vitro, oxygen-glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the LCN2 receptor) was inhibited by astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively. Histological and biochemical analyses were performed to assess astrocyte and neuron death. Additionally, the neurological deficits of mice were evaluated. RESULTS: LCN2 expression was significantly induced in astrocytes 24 h after stroke onset in the mouse MCAO model. Lcn2 knockout (Lcn2-/-) mice exhibited reduced infarct volume and improved neurological and cognitive functions after MCAO. LCN2 and its receptor 24p3R were colocalized in astrocytes. Mechanistically, suppression of 24p3R by AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation and the secretion of pro-inflammatory cytokines via LCN2, which was then reversed by Nig-induced NLRP3 inflammasome activation. Astrocyte pyroptosis was exacerbated in Lcn2-/- mice by intracerebroventricular administration of recombinant LCN2 (rLCN2), while this aggravation was restricted by blocking 24p3R or inhibiting NLRP3 inflammasome activation with MCC950. CONCLUSION: LCN2/24p3R mediates astrocyte pyroptosis via NLRP3 inflammasome activation following cerebral ischemia/reperfusion injury.

The Association between Migraine and Fetal-Type Posterior Cerebral Artery in Patients with Ischemic Stroke.

OBJECTIVE: The aim of the study was to determine if migraine is associated with fetal-type posterior cerebral artery (PCA) in patients with ischemic stroke. METHOD: In this cross-sectional study, patients with acute ischemic stroke were enrolled from two hospitals. The history of migraine headache was evaluated during a face-to-face interview. The variants of fetal-type PCA were assessed with MRA, CTA, or DSA. Patients with and without migraine were compared in terms of fetal-type PCA status and other clinic characteristics. Multivariate logistic regression analyses were performed to adjust for confounders and provide risk estimates for observed associations. RESULT: In 750 patients qualified for analysis, 85 (11.3%) were determined with migraine. Patients with migraine had a higher proportion of female gender (51.8% vs. 31.0%, p < 0.001), hypertension (72.9% vs. 57.7%, p = 0.007), and fetal-type PCA (36.5% vs. 20.1%, p = 0.001), while lower proportion of current smoking (25.9% vs. 38.3%, p = 0.025) than patients without migraine. National Institutes of Health Stroke Scale (NIHSS) score (3 vs. 2, p = 0.016) was also higher in migraineurs than in non-migraineurs. After adjustment for confounders, fetal-type PCA status was independently associated with migraine (odds ratio [OR] = 2.06; 95% confidence interval [CI], 1.25-3.38; p = 0.005). Other factors associated to migraine included female gender (OR = 2.03; 95% CI, 1.13-3.62; p = 0.017), hypertension (OR = 1.97; 95% CI, 1.17-3.34; p = 0.011), and NIHSS score (OR = 1.08; 95% CI, 1.01-1.16; p = 0.018). CONCLUSION: Migraine was associated with fetal-type PCA in patients with ischemic stroke. This finding supported the hypothesis that vascular mechanisms get involved in the migraine-stroke association.

Extracellular vesicles carrying proinflammatory factors may spread atherosclerosis to remote locations.

Most cells involved in atherosclerosis release extracellular vesicles (EVs), which can carry bioactive substances to downstream tissues via circulation. We hypothesized that EVs derived from atherosclerotic plaques could promote atherogenesis in remote locations, a mechanism that mimics the blood metastasis of cancer. Ldlr gene knockout (Ldlr KO) rats were fed on a high cholesterol diet and underwent partial carotid ligation to induce local atherosclerosis. EVs were separated from carotid artery tissues and downstream blood of carotid ligation by centrifugation. MiRNA sequencing and qPCR were then performed to detect miRNA differences in EVs from rats with and without induced carotid atherosclerosis. Biochemical analyses demonstrated that EVs derived from atherosclerosis could increase the expression of ICAM-1, VCAM-1, and E-selectin in endothelial cells in vitro. EVs derived from atherosclerosis contained a higher level of miR-23a-3p than those derived from controls. MiR-23a-3p could promote endothelial inflammation by targeting Dusp5 and maintaining ERK1/2 phosphorylation in vitro. Inhibiting EV release could attenuate atherogenesis and reduce macrophage infiltration in vivo. Intravenously administrating atherosclerotic plaque-derived EVs could induce intimal inflammation, arterial wall thickening and lumen narrowing in the carotids of Ldlr KO rats, while simultaneous injection of miR-23a-3p antagomir could reverse this reaction. The results suggested that EVs may transfer atherosclerosis to remote locations by carrying proinflammatory factors, particularly miR-23a-3p.

Intravenous Thrombolysis before Thrombectomy may Increase the Incidence of Intracranial Hemorrhage inTreating Carotid T Occlusion.

BACKGROUND AND PURPOSE: Current evidence does not agree on the merits of direct and bridging thrombectomy. This study aimed to compare the safety and efficacy of direct thrombectomy (DT) and bridging thrombectomy (BT) in treating patients with acute ischaemic stroke due to carotid T occlusion. METHODS: Patients with stroke due to carotid T occlusion who were treated with DT or BT were retrospectively collected from four advanced stroke centres. Baseline characteristics and clinical outcomes were compared between the groups. Successful recanalization was defined by a modified thrombolysis in cerebral infarction (mTICI) score of 2b or 3. A favourable outcome was defined by a modified Rankin Scale (mRS) score of 0-2 at 90 days after stroke onset. Multivariable analysis was performed to control for potential confounders. RESULTS: Of the 111 enrolled patients, 57 (51.4%) patients were treated with DT, and 54 (48.6%) were treated with BT. Patients treated with DT had a shorter imaging to puncture (ITP) time (53 min versus 92 min, P<0.001) and symptom onset to puncture (OTP) time (198 min versus 218 min, P=0.045) than patients treated with BT. No significant difference was detected concerning the rate of successful recanalization (80.7% versus 77.8%, P=0.704) or a favourable outcome between patients treated with DT and BT (35.1% versus 33.3%, P=0.846). Patients treated with DT had a lower intracranial haemorrhage (ICH) rate (40.4% versus 59.3%, P=0.046), but the difference was not significant for symptomatic ICH (sICH, 12.3% versus 16.7%, P=0.511) or asymptomatic ICH (aICH, 28.1% versus 42.6%, P=0.109). After adjusting for potential confounding factors, the ratio of favorable prognosis, successful reperfusion, sICH and mortality did not differ between the two groups. However, there was a higher rate of ICH (OR=2.492, 95% CI 1.005 to 6.180, p=0.049) in the BT group as compared with the DT group. CONCLUSIONS: DT seems equivalent to BT in treating stroke due to carotid T occlusion in favorable outcome, successful recanalization, 90-day morality and sICH. However, BT may increase the incidence of ICH in this specific type stroke.

Low-density lipoprotein receptor (LDLR) regulates NLRP3-mediated neuronal pyroptosis following cerebral ischemia/reperfusion injury.

BACKGROUND: Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemic stroke. NLRP3 inflammasome, involved in the regulation of inflammatory cascade, can simultaneously lead to GSDMD-executed pyroptosis in cerebral ischemia. Low-density lipoprotein receptor (LDLR), responsible for cholesterol uptake, was noted to exert potential anti-inflammatory bioactivities. Nevertheless, the role of LDLR in neuroinflammation mobilized by cerebral ischemia/reperfusion (I/R) has not been investigated. METHODS: Ischemic stroke mice model was accomplished by middle cerebral artery occlusion. Oxygen-glucose deprivation was employed after primary cortical neuron was extracted and cultured. A pharmacological inhibitor of NLRP3 (CY-09) was administered to suppress NLPR3 activation. Histological and biochemical analysis were performed to assess the neuronal death both in vitro and in vivo. In addition, neurological deficits and behavioral deterioration were evaluated in mice. RESULTS: The expression of LDLR was downregulated following cerebral I/R injury. Genetic knockout of Ldlr enhanced caspase-1-dependent cleavage of GSDMD and resulted in severe neuronal pyroptosis. LDLR deficiency contributed to excessive NLRP3-mediated maturation and release of IL-1ß and IL-18 under in vitro and in vivo ischemic conditions. These influences ultimately led to aggravated neurological deficits and long-term cognitive dysfunction. Blockade of NLRP3 substantially retarded neuronal pyroptosis in Ldlr-/- mice and cultured Ldlr-/- neuron after experimental stroke. CONCLUSIONS: These results demonstrated that LDLR modulates NLRP3-mediated neuronal pyroptosis and neuroinflammation following ischemic stroke. Our findings characterize a novel role for LDLR as a potential therapeutic target in neuroinflammatory responses to acute cerebral ischemic injury.

High-frequency repetitive transcranial magnetic stimulation improves functional recovery by inhibiting neurotoxic polarization of astrocytes in ischemic rats.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment for ischemic stroke. Astrocytes regulation has been suggested as one mechanism for rTMS effectiveness. But how rTMS regulates astrocytes remains largely undetermined. There were neurotoxic and neuroprotective phenotypes of astrocytes (also denoted as classically and alternatively activated astrocytes or A1 and A2 astrocytes) pertaining to pro- or anti-inflammatory gene expression. Pro-inflammatory or neurotoxic polarized astrocytes were induced during cerebral ischemic stroke. The present study aimed to investigate the effects of rTMS on astrocytic polarization during cerebral ischemic/reperfusion injury. METHODS: Three rTMS protocols were applied to primary astrocytes under normal and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Cell survival, proliferation, and phenotypic changes were assessed after 2-day treatment. Astrocytes culture medium (ACM) from control, OGD/R, and OGD/R + rTMS groups were mixed with neuronal medium to culture neurons for 48 h and 7 days, in order to explore the influence on neuronal survival and synaptic plasticity. In vivo, rats were subjected to middle cerebral artery occlusion (MCAO), and received posterior orbital intravenous injection of ACM collected from different groups at reperfusion, and at 3 days post reperfusion. The apoptosis in the ischemic penumbra, infarct volumes, and the modified Neurological Severity Score (mNSS) were evaluated at 1 week after reperfusion, and cognitive functions were evaluated using the Morris Water Maze (MWM) tests. Finally, the 10 Hz rTMS was directly applied to MCAO rats to verify the rTMS effects on astrocytic polarization. RESULTS: Among these three frequencies, the 10 Hz protocol exerted the greatest potential to modulate astrocytic polarization after OGD/R injury. Classically activated and A1 markers were significantly inhibited by rTMS treatment. In OGD/R model, the concentration of pro-inflammatory mediator TNF-α decreased from 57.7 to 23.0 Ñ€g/mL, while anti-inflammatory mediator IL-10 increased from 99.0 to 555.1 Ñ€g/mL in the ACM after rTMS treatment. The ACM collected from rTMS-treated astrocytes significantly alleviated neuronal apoptosis induced by OGD/R injury, and promoted neuronal plasticity. In MCAO rat model, the ACM collected from rTMS treatment decreased neuronal apoptosis and infarct volumes, and improved cognitive functions. The neurotoxic astrocytes were simultaneously inhibited after rTMS treatment. CONCLUSION: Inhibition of neurotoxic astrocytic polarization is a potential mechanism for the effectiveness of high-frequency rTMS in cerebral ischemic stroke.

Human albumin attenuates excessive innate immunity via inhibition of microglial Mincle/Syk signaling in subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke. Microglial macrophage-inducible C-type lectin (Mincle) receptor launches microglial innate immunity after SAH, and thereby achieves a key step of early cerebral injury in SAH. We previously revealed albumin could improve long-term neurological outcomes after SAH. In this study, we examined the role of microglia-mediated innate immunity in the salutary effects of albumin. SAH was induced by endovascular perforation in rats. We found that albumin can significantly mitigate early neurovascular dysfunction of SAH rats. Albumin administration resulted in reduced Iba-1 and CD68 staining in cortex. Markers of microglia M1 polarization (iNOS, IL-1ß, CD16, and CD32) were remarkably suppressed. Neutrophil invasion was inhibited as chemokines (MCP-1, CINC-1, and CXCL-2) mRNA levels, myeloperoxidase (MPO) and intracellular adhesion molecule-1 (ICAM-1) expressions were decreased. Mechanistically, albumin bound with microglial Mincle receptor, and retarded Mincle/Syk/IL-1ß signaling in ipsilateral hemisphere subjected to SAH. In the cultured BV-2 microglial cells, we found Mincle and its ligand SAP130 mediate the cross-talk between neuronal necroptosis and microglial immunity response following SAH-related injury. Albumin could attenuate SAP130-induced Mincle upregulation and subsequent microglial inflammatory responses. The anti-inflammation effect of albumin was similar to the effect of genetic knockdown of Mincle. This effect may be attributed to a direct association between albumin and Mincle. The interaction also yielded a depression in the initiation of Mincle/Syk/IL-1ß pathway. In conclusion, our results indicate that albumin can ameliorate innate immune responses after SAH. This anti-inflammatory action may be through direct restraining microglial Mincle receptor.

Circulating lipocalin-2 as a novel biomarker for early neurological deterioration and unfavorable prognosis after acute ischemic stroke.

INTRODUCTION: Lipocalin-2 (LCN2) is an acute-phase protein that could mediate neuroinflammation after brain injury. We aimed to evaluate if LCN2 level was associated with early neurological deterioration (END) in acute ischemic stroke patients, thus hindering clinical recovery. METHODS: We conducted a prospective study of acute ischemic stroke patients between June 2021 and February 2022. Serum LCN2 concentration was measured after admission using an enzyme-linked immunosorbent assay. Outcomes included END and 90-day poor functional outcome (modified Rankin Scale 3-6). The National Institutes of Health Stroke Scale increment ≥4 points within 72 h after admission was defined as END. RESULTS: A total of 253 acute ischemic stroke patients (mean age, 65.2 ± 13.4 years; 64.0% male) were recruited. In the multivariate adjustment, increased serum LCN2 levels (per 1-SD increase of LCN2) were associated with a higher risk of END (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.20-2.25; p = .002) and 90-day poor outcome (OR, 1.73; 95% CI, 1.22-2.45; p = .002). Restricted cubic splines found a linear relationship between LCN2 level and 90-day unfavorable outcome (END, p = .001 for linearity; 90-day poor outcome, p = .013 for linearity). Subgroup analysis further confirmed the significant association of LCN2 with clinical outcomes. CONCLUSIONS: This study demonstrated that higher circulating LCN2 level was associated with an increased risk of early clinical worsening and 90-day unfavorable outcomes in ischemic stroke patients.

Impacts of stress hyperglycemia ratio on early neurological deterioration and functional outcome after endovascular treatment in patients with acute ischemic stroke.

Background and Purpose: Hyperglycemia has been associated with unfavorable outcome of acute ischemic stroke, but this association has not been verified in patients with endovascular thrombectomy treatment. This study aimed to assess the impact of stress hyperglycemia ratio on early neurological deterioration and favorable outcome after thrombectomy in patients with acute ischemic stroke. Methods: Stroke patients with endovascular thrombectomy in two comprehensive centers were enrolled. Early neurological deterioration was defined as ≥4 points increase of National Institutes of Health Stroke Scale (NIHSS) at 24 hours after endovascular procedure. Favorable outcome was defined as modified Rankin Scale (mRS) score of 0-2 at 90 days of stroke onset. Multivariate regression analysis was used to identify the predictors for early neurological deterioration and favorable outcome. Results: Among the 559 enrolled, 74 (13.2%) patients developed early neurological deterioration. The predictors for early neurological deterioration were high stress hyperglycemia ratio at baseline (OR =5.77; 95% CI, 1.878-17.742; P =0.002), symptomatic intracranial hemorrhage (OR =4.90; 95% CI, 2.439-9.835; P <0.001) and high NIHSS score after 24 hours (OR =1.11; 95% CI, 1.071-1.151; P <0.001). The predictors for favorable outcome were stress hyperglycemia ratio (OR =0.196, 95% CI, 0.077-0.502; P =0.001), age (OR =0.942, 95% CI, 0.909-0.977; P =0.001), NIHSS score 24 hours after onset (OR =0.757, 95% CI =0.693-0.827; P <0.001), groin puncture to recanalization time (OR =0.987, 95% CI, 0.975-0.998; P =0.025), poor collateral status before treatment (ASITN/SIR grade 0-3, OR =62.017, 95% CI, 25.920-148.382; P <0.001), successful recanalization (mTICI 2b or 3, OR =7.415, 95% CI, 1.942-28.313; P =0.001). Conclusion: High stress hyperglycemia ratio may be related to early neurological deterioration and decreased likelihood of favourable outcomes after endovascular thrombectomy in patients with acute ischemic stroke.

Ex Situ Reconstruction-Shaped Ir/CoO/Perovskite Heterojunction for Boosted Water Oxidation Reaction.

The oxygen evolution reaction (OER) is the performance-limiting step in the process of water splitting. In situ electrochemical conditioning could induce surface reconstruction of various OER electrocatalysts, forming reactive sites dynamically but at the expense of fast cation leaching. Therefore, achieving simultaneous improvement in catalytic activity and stability remains a significant challenge. Herein, we used a scalable cation deficiency-driven exsolution approach to ex situ reconstruct a homogeneous-doped cobaltate precursor into an Ir/CoO/perovskite heterojunction (SCI-350), which served as an active and stable OER electrode. The SCI-350 catalyst exhibited a low overpotential of 240 mV at 10 mA cm-2 in 1 M KOH and superior durability in practical electrolysis for over 150 h. The outstanding activity is preliminarily attributed to the exponentially enlarged electrochemical surface area for charge accumulation, increasing from 3.3 to 175.5 mF cm-2. Moreover, density functional theory calculations combined with advanced spectroscopy and 18O isotope-labeling experiments evidenced the tripled oxygen exchange kinetics, strengthened metal-oxygen hybridization, and engaged lattice oxygen oxidation for O-O coupling on SCI-350. This work presents a promising and feasible strategy for constructing highly active oxide OER electrocatalysts without sacrificing durability.

Inverted U-shaped Relationship Between Mean Platelet Volume/Platelet Count Ratio and Post-thrombolytic Early Neurological Deterioration in Patients with Mild and Moderate Stroke.

OBJECTIVE: The objective of this study is to investigate the relationship between mean platelet volume (MPV)/platelet count (PC) ratio and post-thrombolytic early neurological deterioration (END) in patients with mild and moderate stroke. METHODS: Mild and moderate stroke patients treated with intravenous thrombolysis (IVT) at the Affiliated Changsha Central Hospital of the University of South China between January 2016 and March 2022 were prospectively and consecutively enrolled. END was defined as an increase in the total National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points or an increase in the motor items of ≥1 point within 24 hours after IVT treatment. Logistic regression and restricted cubic spline models were used to estimate the relationship between the MPV/PC ratio and postthrombolytic END. RESULTS: Among the 406 patients recruited, 64 (15.8%) patients developed END. Patients in the first quintile of MPV/PC ratio (adjusted OR = 0.27, 95% CI = 0.11-0.66, p = 0.004) and the fifth quintile (adjusted OR = 0.26, 95% CI = 0.10-0.69, p = 0.007) had a significantly lower risk of END compared with those in the third quintile. Restricted cubic spline analysis revealed an inverted U-shaped relationship between the MPV/PC ratio and END (p for nonlinearity = 0.016). MPV/PC ratio cut-off value associated with the highest END risk was 51.0. An MPV/PC ratio ≤ 51.0 was shown to be positively associated with END (adjusted OR = 1.07, 95% CI = 1.02-1.14, p = 0.012), while an MPV/PC ratio >51.0 was negatively associated with END (adjusted OR = 0.94, 95% CI = 0.88-1.00, p = 0.040). A significant interaction existed between the MPV/PC ratio and age in the low MPV/PC ratio group (p = 0.012). MPV/PC ratio was positively associated with END only in patients ≥ 60 years, whereas this association was insignificant in patients < 60 years. CONCLUSION: An inverted U-shaped relationship between the MPV/PC ratio on admission and postthrombolytic END was identified in patients with mild and moderate stroke, with a threshold MPV/PC ratio of 51.0. The MPV/PC ratio closer to the threshold was associated with a higher risk of post-thrombolytic END.

Keys Unlocking Redispersion of Reactive PdOx Nanoclusters on Ce-Functionalized Perovskite Oxides for Methane Activation.

Nowadays, trace CH4 emitted from vehicle exhausts severely threaten the balance of the ecology system of our earth. Thereby, the development of active and stable catalysts capable of methane conversion under mild conditions is critical. Here, we present a convenient method to redisperse catalytically inert PdO nanoparticles (NPs) (>10 nm) into reactive PdOx nanoclusters (∼2 nm) anchored on a Ce-doped LaFeO3 parent. Isothermally activated in an N2 flow, the redispersed catalyst achieved a CH4 conversion of 90% at 400 °C, which is significantly higher than the fresh and H2- and O2-treated counterparts (625, 616, and 641 °C, respectively), indicating the importance of the gas atmosphere in the redispersion of PdO NPs. In addition, the comprehensive catalyst characterizations demonstrated that the isolated Ce ions in the perovskite lattice play an irreplaceable role in the redispersion of reactive sites and the reduction of the energy barrier for C-H scission. More importantly, the Ce additive helps to stabilize the PdOx species by reducing overoxidation, resulting in significant lifetime extension. Through a thorough understanding of structural manipulation, this study sheds light on the design of highly performing supported catalysts for methane oxidation.

A non-contrast computed tomography-based radiomics nomogram for the prediction of hematoma expansion in patients with deep ganglionic intracerebral hemorrhage.

Background and purpose: Hematoma expansion (HE) is a critical event following acute intracerebral hemorrhage (ICH). We aimed to construct a non-contrast computed tomography (NCCT) model combining clinical characteristics, radiological signs, and radiomics features to predict HE in patients with spontaneous ICH and to develop a nomogram to assess the risk of early HE. Materials and methods: We retrospectively reviewed 388 patients with ICH who underwent initial NCCT within 6 h after onset and follow-up CT within 24 h after initial NCCT, between January 2015 and December 2021. Using the LASSO algorithm or stepwise logistic regression analysis, five models (clinical model, radiological model, clinical-radiological model, radiomics model, and combined model) were developed to predict HE in the training cohort (n = 235) and independently verified in the test cohort (n = 153). The Akaike information criterion (AIC) and the likelihood ratio test (LRT) were used for comparing the goodness of fit of the five models, and the AUC was used to evaluate their ability in discriminating HE. A nomogram was developed based on the model with the best performance. Results: The combined model (AIC = 202.599, χ2 = 80.6) was the best fitting model with the lowest AIC and the highest LRT chi-square value compared to the clinical model (AIC = 232.263, χ2 = 46.940), radiological model (AIC = 227.932, χ2 = 51.270), clinical-radiological model (AIC = 212.711, χ2 = 55.490) or radiomics model (AIC = 217.647, χ2 = 57.550). In both cohorts, the nomogram derived from the combined model showed satisfactory discrimination and calibration for predicting HE (AUC = 0.900, sensitivity = 83.87%; AUC = 0.850, sensitivity = 80.10%, respectively). Conclusion: The NCCT-based model combining clinical characteristics, radiological signs, and radiomics features could efficiently discriminate early HE, and the nomogram derived from the combined model, as a non-invasive tool, exhibited satisfactory performance in stratifying HE risks.

Malnutrition and Risk of Mortality in Ischemic Stroke Patients Treated With Intravenous Thrombolysis.

Background and Purpose: Malnutrition is highly prevalent in ischemic stroke patients. We aimed to investigate whether malnutrition indexes may be useful in predicting mortality at 90 days in ischemic stroke patients treated with intravenous thrombolysis. Methods: We retrospectively analyzed consecutive patients who underwent thrombolytic therapy at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). Results: Of 979 patients (mean age, 66.8 years; males, 63.6%) included in this study, 91 (9.3%; 95% confidence interval [CI]: 8.4-10.2%) died at 3-month follow up. According to the CONUT, GNRI, and PNI scores, 9.9, 33.7, and 7.0% of patients were moderately or severely malnourished, respectively; 64.0% were at least mildly malnourished by at least 1 malnutrition index. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of mortality for CONUT scores (adjusted odds ratio [OR] 16.16, 95%CI, 7.86-67.11; P < 0.001), GNRI scores (adjusted OR 9.82, 4.10-23.51; P < 0.001) and PNI scores (adjusted OR 12.74, 5.56-29.19; P < 0.001). Similar results were found when the malnutrition scores were analyzed as continuous variables. Adding the three malnutrition indexes to models containing conventional risk factors significantly improved risk reclassification for 3-month mortality. Conclusion: Our study showed that malnutrition may be associated with a higher risk of mortality at 3 months in ischemic stroke after intravenous thrombolysis.

Atomic cerium modulated palladium nanoclusters exsolved ferrite catalysts for lean methane conversion.

The active and stable palladium (Pd) based catalysts for CH4 conversion are of great environmental and industrial significance. Herein, we employed N2 as an optimal activation agent to develop a Pd nanocluster exsolved Ce-incorporated perovskite ferrite catalyst toward lean methane oxidation. Replacing the traditional initiator of H2, the N2 was found as an effective driving force to selectively touch off the surface exsolution of Pd nanocluster from perovskite framework without deteriorating the overall material robustness. The catalyst showed an outstanding T50 (temperature of 50% conversion) plummeting down to 350°C, outperforming the pristine and H2-activated counterparts. Further, the combined theoretical and experimental results also deciphered the crucial role that the atomically dispersed Ce ions played in both construction of active sites and CH4 conversion. The isolated Ce located at the A-site of perovskite framework facilitated the thermodynamic and kinetics of the Pd exsolution process, lowering its formation temperature and promoting its quantity. Moreover, the incorporation of Ce lowered the energy barrier for cleavage of C─H bond, and was dedicated to the preservation of highly reactive PdOx moieties during stability measurement. This work successfully ventures uncharted territory of in situ exsolution to provide a new design thinking for a highly performed catalytic interface.

A Nomogram to Predict Symptomatic Intracranial Hemorrhage After Intravenous Thrombolysis in Chinese Patients.

BACKGROUND AND AIMS: A reliable predictive score system to identify the risk of symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis (IVT) in acute ischemic stroke patients is of great essence. We aimed to develop a nomogram for predicting the risk of sICH after IVT in Chinese patients. METHODS: We recruited acute ischemic stroke patients who were treated with IVT from five advanced stroke centers in China from April 2014 to November 2020. sICH was diagnosed according to the European Cooperative Acute Stroke Study II (ECASS-II) definition. Multivariable logistic regression was performed to construct the best-fit nomogram. The discrimination and calibration of the nomogram were evaluated by the area under the receiver operating characteristic curve (AUC-ROC) and calibration plot. RESULTS: A total of 1200 patients were enrolled, of whom 66 (5.5%) developed sICH. In the multivariate logistic regression model, atrial fibrillation (odds ratio [OR] 3.25; 95% confidence interval [CI], 1.89-5.60; P < 0.001), baseline glucose level (OR, 1.13; 95% CI, 1.07-1.20; P < 0.001), neutrophil to lymphocyte ratio (OR, 1.05; 95% CI, 1.01-1.09; P = 0.024) and baseline National Institute of Health Stroke Scale (NIHSS) (OR, 1.07; 95% CI, 1.04-1.10; P < 0.001) were independent predictors for sICH and were used to generate the nomogram. The nomogram demonstrated good discrimination as the AUC-ROC value was 0.788 (95% CI, 0.737-0.840). The calibration plot revealed good calibration. CONCLUSION: The nomogram consisted of atrial fibrillation, baseline glucose level, neutrophil to lymphocyte ratio, and NIHSS score may predict the risk of sICH in Chinese acute ischemic stroke patients treated with IVT.

Unusual Role of Point Defects in Perovskite Nickelate Electrocatalysts.

Low-cost transition-metal oxide is regarded as a promising electrocatalyst family for an oxygen evolution reaction (OER). The classic design principle for an oxide electrocatalyst believes that point defect engineering, such as oxygen vacancies (VO..) or heteroatom doping, offers the opportunities to manipulate the electronic structure of material toward optimal OER activity. Oppositely, in this work, we discover a counterintuitive phenomenon that both VO.. and an aliovalent dopant (i.e., proton (H+)) in perovskite nickelate (i.e., NdNiO3 (NNO)) have a considerably detrimental effect on intrinsic OER performance. Detailed characterizations unveil that the introduction of these point defects leads to a decrease in the oxidative state of Ni and weakens Ni-O orbital hybridization, which triggers the local electron-electron correlation and a more insulating state. Evidenced by first-principles calculation using the density functional theory (DFT) method, the OER on nickelate electrocatalysts follows the lattice oxygen mechanism (LOM). The incorporation of point defect increases the energy barrier of transformation from OO*(VO) to OH*(VO) intermediates, which is regarded as the rate-determining step (RDS). This work offers a new and significant perspective of the role that lattice defects play in the OER process.

Serum Albumin Levels and Clinical Outcomes Among Ischemic Stroke Patients Treated with Endovascular Thrombectomy.

BACKGROUND AND AIMS: Albumin levels have been reported to be associated with all-cause and cardiovascular mortality. The aim of this study was to investigate the association between serum albumin and prognosis of ischemic stroke patients after endovascular thrombectomy (EVT) treatment. METHODS: Patients with EVT due to large artery occlusion in anterior circulation were selected from ACTUAL (endovascular treatment for acute anterior circulation) ischemic stroke multicenter registry in China. Serum albumin levels were measured within 24 h of admission. The primary outcome was poor functional outcome (modified Rankin scale score of 3-6) at three months. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and three-month mortality. RESULTS: A total of 605 patients (mean age, 64.2 years; 59.3% male) were enrolled. Up to three months after stroke, 342 patients (56.5%) developed poor functional outcome. After multivariate adjustment for demographic characteristics, National Institutes of Health stroke score, and other potential confounders, the odds ratio for the lowest tertile of serum albumin levels was 2.43 (95%CI, 1.18-5.01; P=0.046) for poor functional outcome, compared with the highest category. Restricted cubic spline regression demonstrated a linear association between albumin levels and poor functional outcome (P for linearity=0.017). Subgroup analyses further confirmed these results. Similar significant findings were also found in the association of serum albumin with mortality, but not with sICH. CONCLUSION: Decreased serum albumin levels were independently associated with poor prognosis at 90 days after acute large vessel occlusion stroke in anterior circulation treated with EVT.

Blood pressure variability and outcomes after mechanical thrombectomy based on the recanalization and collateral status.

BACKGROUND: Blood pressure (BP), recanalization status, and collateral circulation are important factors for cerebral autoregulation after stroke. We aimed to investigate the association of various BP variability (BPV) parameters with clinical outcomes after mechanical thrombectomy (MT) according to recanalization and collateral status. METHODS: We included 502 consecutive patients who underwent MT due to anterior circulation large vessel occlusion stroke at three comprehensive stroke centers. BPV parameters were standard deviation (SD), maximum/minimum BP, coefficient of variation (CV) and successive variation (SV). The clinical outcomes included 90-day functional outcome assessed by modified Rankin Scale score and symptomatic intracranial hemorrhage (sICH). RESULTS: Among the included patients, 219 (43.6%) achieved good functional outcomes and 59 (11.8%) developed sICH. After adjusting for confounders, higher systolic BP (SBP) variability [CV (odds ratio (OR), 1.089, p = 0.035), SV (OR, 1.082, p = 0.004). and SD (OR, 1.074, p = 0.027)] was associated with a lower likelihood of a favorable outcome. In addition, higher SBP [CV (OR, 1.156, p = 0.001) and SD (OR, 1.118, p = 0.001)] were significantly associated with increased odds of sICH. Moreover, the relationship between BPV and the outcomes depended on recanalization status. However, regardless of collateral status, a higher BPV after MT was associated with worse outcomes. CONCLUSIONS: Higher SBP SD and CV during the first 24 h after MT was a powerful predictor of worse clinical outcomes, regardless of the collateral status. However, the effects of BPV on outcomes were more substantial among patients with successful reperfusion.