Intra-arterial tenecteplase after successful endovascular therapy (ANGEL-TNK): protocol of a multicentre, open-label, blinded end-point, prospective, randomised trial.

BACKGROUND: Despite successful reperfusion after thrombectomy for large vessel occlusion (LVO) stroke, up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to demonstrate safety and efficacy of administering adjunct intra-arterial (IA) tenecteplase in anterior circulation LVO patients who have achieved successful reperfusion defined as eTICI 2b50 to 3. METHODS: ANGEL-TNK is a multicentre, open-label, assessor-blinded endpoint, prospective randomised, controlled trial that will enrol up to 256 patients. Patients who meet inclusion criteria with anterior circulation LVO stroke and successful reperfusion will be randomised to receive IA tenecteplase or best medical management at 1:1 ratio. RESULTS: The primary endpoint is a 90-day excellent outcome defined as modified Rankin Scale (mRS) 0-1. The primary safety endpoint is symptomatic intracranial haemorrhage within 48 hours from randomisation. Secondary endpoints include 90-day ordinal mRS, mRS 0-2, mRS 0-3, all-cause mortality and any intracranial haemorrhage. CONCLUSION: In patients with anterior circulation LVO stroke, the ANGEL-TNK trial will inform whether adjunct IA tenecteplase administered after successful thrombectomy reperfusion improves patient outcomes. TRIAL REGISTRATION NUMBER: NCT05624190.

Electrical Response of Different Crystalline Microregions in Poly(vinylidene fluoride).

The crystal structure has a great influence on the dielectric and piezoelectric performance of poly(vinylidene fluoride) (PVDF). In this work, we prepared PVDF films with two typical crystalline phases (α and ß). In situ Kelvin probe force microscopy (KPFM) and Piezoelectric force microscopy (PFM) were employed to investigate the responses of different PVDF crystalline phases to charge mobility, polarization, and piezoelectric properties. We used a homemade Kelvin probe force microscope (KPFM) to inject charges into the two crystalline phases to investigate the differences in the response of different crystalline phases of PVDF to electrical excitation on a microscopic scale. It was found that the α-phase has a lower charge injection barrier and is more susceptible to charge injection and that the α-phase is accompanied by a faster charge dissipation rate, which makes it easier to accumulate charge at the interface between the α-phase and ß-phase PVDF. Moreover, the PFM polarization manipulation showed no change in the amplitude and phase diagram of the α-phase under ±10 V bias. In contrast, the ß-phase showed a clear polarization reversal phenomenon and a significant increase in piezoelectric amplitude, which is consistent with its polar intrinsic properties. This study provides valuable insights into the multiphase contributions and a reference for designing advanced PVDF dielectrics.

Artificial intelligence-assisted oculo-gait measurements for cognitive impairment in cerebral small vessel disease.

INTRODUCTION: Oculomotor and gait dysfunctions are closely associated with cognition. However, oculo-gait patterns and their correlation with cognition in cerebral small vessel disease (CSVD) remain unclear. METHODS: Patients with CSVD from a hospital-based cohort (n = 194) and individuals with presumed early CSVD from a community-based cohort (n = 319) were included. Oculo-gait patterns were measured using the artificial intelligence (AI) -assisted 'EyeKnow' eye-tracking and 'ReadyGo' motor evaluation systems. Multivariable linear and logistic regression models were employed to investigate the association between the oculo-gait parameters and cognition. RESULTS: Anti-saccade accuracy, stride velocity, and swing velocity were significantly associated with cognition in both patients and community dwellers with CSVD, and could identify cognitive impairment in CSVD with moderate accuracy (area under the curve [AUC]: hospital cohort, 0.787; community cohort, 0.810) after adjusting for age and education. DISCUSSION: The evaluation of oculo-gait features (anti-saccade accuracy, stride velocity, and swing velocity) may help screen cognitive impairment in CSVD. HIGHLIGHTS: Oculo-gait features (lower anti-saccade accuracy, stride velocity, and swing velocity) were associated with cognitive impairment in cerebral small vessel disease (CSVD). Logistic model integrating the oculo-gait features, age, and education level moderately distinguished cognitive status in CSVD. Artificial intelligence-assisted oculomotor and gait measurements provide quick and accurate evaluation in hospital and community settings.

Unveiling connections between venous disruption and cerebral small vessel disease using diffusion tensor image analysis along perivascular space (DTI-ALPS): A 7T MRI study.

BACKGROUND: Cerebral venous disruption is one of the characteristic findings in cerebral small vessel disease (CSVD), and its disruption may impede perivascular glymphatic drainage. And lower diffusivity along perivascular space (DTI-ALPS) index has been suggested to be with the presence and severity of CSVD. However, the relationships between venous disruption, DTI-ALPS index, and CSVD neuroimaging features remain unclear. AIMS: To investigate the association between venous integrity and perivascular diffusion activity, and explore the mediating role of DTI-ALPS index between venous disruption and CSVD imaging features. METHODS: In this cross-sectional study, 31 patients (mean age, 59.0 ± 9.9 years) were prospectively enrolled and underwent 7T MR imaging. DTI-ALPS index was measured to quantify the perivascular diffusivity. The visibility and continuity of deep medullary veins (DMVs) were evaluated based on a brain region-based visual score on high-resolution susceptibility weighted imaging. White matter hyperintensity (WMH) and perivascular space (PVS) were assessed using qualitative and quantitative methods. Linear regression and mediation analysis were performed to analyze the relationships among DMV scores, DTI-ALPS index, and CSVD features. RESULTS: The DTI-ALPS index was significantly associated with the parietal DMV score [ß = -0.573, p-corrected = 0.004]. Parietal DMV score was associated with WMH volume [ß = 0.463, p-corrected = 0.013] and PVS volume in basal ganglia (ß = 0.415, p-corrected = 0.028]. Mediation analyses showed that DTI-ALPS index manifested a full mediating effect on the association between parietal DMV score and WMH (indirect effect = 0.115, Pm=43.1%), as well as between parietal DMV score and PVS volume in basal ganglia (indirect effect = 0.161, Pm=42.8%). CONCLUSIONS: Cerebral venous disruption is associated with glymphatic activity, and with WMH and PVS volumes. Our results suggest cerebral venous integrity may play a critical role in preserving perivascular glymphatic activity; while disruption of small veins may impair the perivascular diffusivity, thereby contributing to the development of WMH and PVS enlargement.

Potential preservative mechanisms of cardiac rehabilitation pathways on endothelial function in coronary heart disease.

Cardiac rehabilitation, a comprehensive exercise-based lifestyle and medical management, is effective in decreasing morbidity and improving life quality in patients with coronary heart disease. Endothelial function, an irreplaceable indicator in coronary heart disease progression, is measured by various methods in traditional cardiac rehabilitation pathways, including medicinal treatment, aerobic training, and smoking cessation. Nevertheless, studies on the effect of some emerging cardiac rehabilitation programs on endothelial function are limited. This article briefly reviewed the endothelium-beneficial effects of different cardiac rehabilitation pathways, including exercise training, lifestyle modification and psychological intervention in patients with coronary heart disease, and related experimental models, and summarized both uncovered and potential cellular and molecular mechanisms of the beneficial roles of various cardiac rehabilitation pathways on endothelial function. In exercise training and some lifestyle interventions, the enhanced bioavailability of nitric oxide, increased circulating endothelial progenitor cells (EPCs), and decreased oxidative stress are major contributors to preventing endothelial dysfunction in coronary heart disease. Moreover, the preservation of endothelial-dependent hyperpolarizing factors and inflammatory suppression play roles. On the one hand, to develop more endothelium-protective rehabilitation methods in coronary heart disease, adequately designed and sized randomized multicenter clinical trials should be advanced using standardized cardiac rehabilitation programs and existing assessment methods. On the other hand, additional studies using suitable experimental models are warranted to elucidate the relationship between some new interventions and endothelial protection in both macro- and microvasculature.

Slowdown in China's methane emission growth.

The unprecedented surge in global methane levels has raised global concerns in recent years, casting a spotlight on China as a pivotal emitter. China has taken several actions to curb the methane emissions, but their effects remain unclear. Here, we developed the Global ObservatioN-based system for monitoring Greenhouse GAses for methane (GONGGA-CH4) and assimilate GOSAT XCH4 observations to assess changes in China's methane emissions. We find the average rate of increase in China's methane emissions (0.1 ± 0.3 Tg CH4 yr-2) during 2016-2021 slowed down compared to the preceding years (2011-2015) (0.9 ± 0.5 Tg CH4 yr-2), in contrast to the concurrent acceleration of global methane emissions. As a result, the contribution of China to global methane emissions dropped significantly. Notably, the slowdown of China's methane emission is mainly attributable to a reduction in biogenic emissions from wetlands and agriculture, associated with the drying trend in South China and the transition from double-season to single-season rice cropping, while fossil fuel emissions are still increasing. Our results suggest that GONGGA-CH4 provides the opportunity for independent assessment of China's methane emissions from an atmospheric perspective, providing insights into the implementation of methane-related policies that align with its ambitious climate objectives.

Relationships between brain structure-function coupling in normal aging and cognition: A cross-ethnicity population-based study.

Increased efforts in neuroscience seek to understand how macro-anatomical and physiological connectomes cooperatively work to generate cognitive behaviors. However, the structure-function coupling characteristics in normal aging individuals remain unclear. Here, we developed an index, the Coupling in Brain Structural connectome and Functional connectome (C-BSF) index, to quantify regional structure-function coupling in a large community-based cohort. C-BSF used diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) data from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events study (PRECISE) cohort (2007 individuals, age: 61.15 ± 6.49 years) and the Sydney Memory and Ageing Study (MAS) cohort (254 individuals, age: 83.45 ± 4.33 years). We observed that structure-function coupling was the strongest in the visual network and the weakest in the ventral attention network. We also observed that the weaker structure-function coupling was associated with increased age and worse cognitive level of the participant. Meanwhile, the structure-function coupling in the visual network was associated with the visuospatial performance and partially mediated the connections between age and the visuospatial function. This work contributes to our understanding of the underlying brain mechanisms by which aging affects cognition and also help establish early diagnosis and treatment approaches for neurological diseases in the elderly.

Copper dual-doping strategy of porous carbon nanofibers and nickel fluoride nanorods as bi-functional oxygen electrocatalysis for effective zinc-air batteries.

Designing and developing efficient, low-cost bi-functional oxygen electrocatalysts is essential for effective zinc-air batteries. In this study, we propose a copper dual-doping strategy, which involves doping both porous carbon nanofibers (PCNFs) and nickel fluoride nanoparticles with copper alone, successfully preparing copper-doped nickel fluoride (NiF2) nanorods and copper nanoparticles co-modified PCNFs (Cu@NiF2/Cu-PCNFs) as an efficient bi-functional oxygen electrocatalyst. When copper is doped into the PCNFs in the form of metallic nanoparticles, the doped elemental copper can improve the electronic conductivity of composite materials to accelerate electron conduction. Meanwhile, the copper doping for NiF2 can significantly promote the transformation of nickel fluoride nanoparticles into nanorod structures, thus increasing the electrochemical active surface area and enhancing mass diffusion. The Cu-doped NiF2 nanorods also possess an optimized electronic structure, including a more negative d-band center, smaller bandgap width and lower reaction energy barrier. Under the synergistic effect of these advantages, the obtained Cu@NiF2/Cu-PCNFs exhibit outstanding bi-functional catalytic performances, with a low overpotential of 0.68 V and a peak power density of 222 mW cm-2 in zinc-air batteries (ZABs) and stable cycling for 800 h. This work proposes a one-step way based on the dual-doping strategy, providing important guidance for designing and developing efficient catalysts with well-designed architectures for high-performance ZABs.

The Initial Clinical and Electrophysiological Characteristics of Different Subtypes of Guillain-Barré Syndrome Diagnosed Based on Serial Electrophysiological Examinations.

BACKGROUND: We aimed to identify different Guillain-Barré syndrome (GBS) subtypes, demyelination, axonal degeneration, and reversible conduction failure (RCF) as early as possible by analyzing the initial clinical and electrophysiological examinations. METHODS: This study retrospectively collected GBS patients between October 2018 and December 2022 at Beijing Tiantan Hospital. The diagnostic criteria for the initial electrophysiological study were based on Rajabally's criteria, and the criteria for the serial electrophysiological study were based on Uncini's criteria. All subjects underwent clinical and electrophysiological evaluations at least twice within 8 weeks. RESULTS: A total of 47 eligible patients with GBS were included, comprising 19 acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 18 axonal degenerations, and 10 RCFs. In the RCF group, 40%, 30%, and 30% patients were diagnosed as AIDP, axonal, and equivocal at the initial study, respectively. The AIDP group had significantly higher cerebrospinal fluid (CSF) protein than the RCF (123.8 [106.4, 215.1] mg/dL vs. 67.1 [36.8, 85.6] mg/dL, p = 0.002) and axonal degeneration (123.8 [106.4, 215.1] mg/dL vs. 60.8 [34.8, 113.0] mg/dL, p < 0.001) groups. The RCF group had significantly lower Hughes functional grades at admission (3 [2, 4] vs. 4 [4, 4], p = 0.012) and discharge (1.0 [1.0, 2.0] vs. 3.0 [2.0, 3.0], p < 0.001) than the axonal degeneration group and showed significantly shorter distal motor latency (DML), Fmin, Fmean, Fmax, and lower F% than the AIDP group (p < 0.05). DISCUSSION: The early identification of RCF from AIDP had relatively obvious features, including slightly elevated CSF protein levels and normal or slightly prolonged DML and F-wave latencies, contrasting with the apparent elevation and prolongation seen in AIDP. Differentiating RCF from axonal degeneration remains challenging. One potential distinguishing factor is that the motor function in RCF tends to be better than in the latter.

Clopidogrel and Aspirin Initiated Between 24 to 72 Hours for Mild Ischemic Stroke: A Subgroup Analysis of the INSPIRES Randomized Clinical Trial.

Importance: Prior trials showed that dual antiplatelet therapy could reduce the risk of early new stroke in patients with acute mild ischemic stroke or transient ischemic attack (TIA) within 24 hours of symptom onset. However, it is currently uncertain whether dual antiplatelet therapy can reduce the risk of early new stroke in patients with a more delayed initiation time window. Objective: To evaluate the efficacy and safety of clopidogrel and aspirin among patients with mild ischemic stroke or TIA when initiated within 24 hours, from more than 24 hours to 48 hours, and from more than 48 hours to 72 hours. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial randomized clinical trial conducted at 222 hospitals in China from September 17, 2018, to October 15, 2022. All patients with acute mild ischemic stroke and TIA were included in this subgroup analysis and categorized into 3 groups according to time from symptom onset to randomization (group 1: ≤24 hours; group 2: >24 to ≤48 hours; and group 3: >48 to 72 hours). Patients were followed up for 90 days. Interventions: All patients received clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90, and aspirin 100 to 300 mg on the first day and then 100 mg daily for days 2 to 90) or aspirin alone (100 to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset. Main Outcomes and Measures: The primary outcome was new stroke (ischemic or hemorrhagic) within 90 days. The primary safety outcome was moderate-to-severe bleeding, according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria. Results: This analysis included a total of 6100 patients (3050 in the clopidogrel-aspirin group and 3050 in the aspirin group). The median age was 65 years (IQR, 57-71 years), and 3915 patients (64.2%) were male. In the population with time to randomization of 24 hours or less, stroke occurred in the next 90 days in 97 of 783 patients (12.4%); among those randomized from more than 24 hours to 48 hours, in 211 of 2552 patients (8.3%) among those randomized from more than 24 hours to 48 hours, and in 193 of 2765 patients (7.0%). The clopidogrel-aspirin group had a lower risk of new stroke within 90 days compared with the aspirin alone group both in patients with time to randomization of from 48 to 72 hours (5.8% vs 8.2%; hazard ratio [HR], 0.70 [95% CI, 0.53-0.94]), of more than 24 to 48 hours (7.6% vs 8.9%; HR, 0.85 [95% CI, 0.65-1.12]), and of 24 hours or less (11.5% vs 13.4%; HR, 0.83 [95% CI, 0.55-1.25]) (P = .38 for interaction). Among those with time to randomization of more than 48 to 72 hours, moderate-to-severe bleeding occurred in 12 patients (0.9%) in the clopidogrel-aspirin group and in 6 patients (0.4%) in the aspirin-alone group (HR, 2.00 [95% CI, 0.73-5.43]), while moderate-to-severe bleeding in those with time to randomization of more than 24 hours to 48 hours occurred in 9 patients (0.7%) in the clopidogrel-aspirin group and in 4 patients (0.3%) in the aspirin-alone group (HR, 2.25 [95% CI, 0.68-7.39]) and in those with time to randomization of within 24 hours, occurred in 6 patients (1.5%) in the clopidogrel-aspirin group and in 3 patients (0.8%) in the aspirin-alone group (HR, 1.57 [95% CI, 0.36-6.83]) (P = .92 for interaction). Conclusions and Relevance: In this randomized clinical trial of antiplatelet therapy in China, patients with mild ischemic stroke or TIA had consistent benefit from dual antiplatelet therapy with clopidogrel and aspirin vs aspirin alone when initiated within 72 hours after symptom onset, with a similar increase in the risk of moderate-to-severe bleeding. Patients should receive dual antiplatelet therapy with clopidogrel and aspirin within 72 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.

Balloon Angioplasty vs Medical Management for Intracranial Artery Stenosis: The BASIS Randomized Clinical Trial.

Importance: Previous randomized clinical trials did not demonstrate the superiority of endovascular stenting over aggressive medical management for patients with symptomatic intracranial atherosclerotic stenosis (sICAS). However, balloon angioplasty has not been investigated in a randomized clinical trial. Objective: To determine whether balloon angioplasty plus aggressive medical management is superior to aggressive medical management alone for patients with sICAS. Design, Setting, and Participants: A randomized, open-label, blinded end point clinical trial at 31 centers across China. Eligible patients aged 35 to 80 years with sICAS defined as recent transient ischemic attack (<90 days) or ischemic stroke (14-90 days) before enrollment attributed to a 70% to 99% atherosclerotic stenosis of a major intracranial artery receiving treatment with at least 1 antithrombotic drug and/or standard risk factor management were recruited between November 8, 2018, and April 2, 2022 (final follow-up: April 3, 2023). Interventions: Submaximal balloon angioplasty plus aggressive medical management (n = 249) or aggressive medical management alone (n = 252). Aggressive medical management included dual antiplatelet therapy for the first 90 days and risk factor control. Main Outcomes and Measures: The primary outcome was a composite of any stroke or death within 30 days after enrollment or after balloon angioplasty of the qualifying lesion or any ischemic stroke in the qualifying artery territory or revascularization of the qualifying artery after 30 days through 12 months after enrollment. Results: Among 512 randomized patients, 501 were confirmed eligible (mean age, 58.0 years; 158 [31.5%] women) and completed the trial. The incidence of the primary outcome was lower in the balloon angioplasty group than the medical management group (4.4% vs 13.5%; hazard ratio, 0.32 [95% CI, 0.16-0.63]; P < .001). The respective rates of any stroke or all-cause death within 30 days were 3.2% and 1.6%. Beyond 30 days through 1 year after enrollment, the rates of any ischemic stroke in the qualifying artery territory were 0.4% and 7.5%, respectively, and revascularization of the qualifying artery occurred in 1.2% and 8.3%, respectively. The rate of symptomatic intracranial hemorrhage in the balloon angioplasty and medical management groups was 1.2% and 0.4%, respectively. In the balloon angioplasty group, procedural complications occurred in 17.4% of patients and arterial dissection occurred in 14.5% of patients. Conclusions and Relevance: In patients with sICAS, balloon angioplasty plus aggressive medical management, compared with aggressive medical management alone, statistically significantly lowered the risk of a composite outcome of any stroke or death within 30 days or an ischemic stroke or revascularization of the qualifying artery after 30 days through 12 months. The findings suggest that balloon angioplasty plus aggressive medical management may be an effective treatment for sICAS, although the risk of stroke or death within 30 days of balloon angioplasty should be considered in clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03703635.

Duration of Benefit and Risk of Dual Antiplatelet Therapy up to 72 Hours After Mild Ischemic Stroke and Transient Ischemic Attack.

BACKGROUND AND OBJECTIVES: Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients. METHODS: The INSPIRES trial was a 2*2 factorial placebo-controlled randomized trial conducted in 222 hospitals in China. The 2 treatments did not interact and were evaluated separately. In this study, we performed secondary analyses based on antiplatelet treatment. All patients with mild stroke or TIA of presumed atherosclerotic cause within 72 hours of symptom onset enrolled in the trial were included. Patients were randomly assigned to receive clopidogrel-aspirin on days 1-21 followed by clopidogrel on days 22-90 or aspirin alone for 90 days. The primary efficacy outcome was major ischemic event which included the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was moderate-to-severe bleeding. We estimated the risk difference between the 2 treatments for each stratified week. RESULTS: All 6,100 patients in the trial were included (3,050 in each group). The mean age was 65 years, and 3,915 patients (64.2%) were men. Compared with aspirin alone, the reduction of major ischemic events by clopidogrel-aspirin mainly occurred in the first week (absolute risk reduction [ARR] 1.42%, 95% CI 0.53%-2.32%) and remained in the second week (ARR 0.49%, 95% CI 0.09%-0.90%) and the third week (ARR 0.29%, 95% CI -0.05% to 0.62%). Numerical higher risk of moderate-to-severe bleedings in the clopidogrel-aspirin group was observed in the first 3 weeks (absolute risk increase 0.05% [95% CI -0.10% to 0.20%], 0.10% [95% CI -0.09% to 0.29%], and 0.18% [95% CI -0.03% to 0.40%] in the first, second, and third weeks, respectively). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low, but ongoing hemorrhagic risk. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03635749. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low but ongoing hemorrhagic risk.

Glycated albumin levels are associated with adverse stroke outcomes in patients with acute ischemic stroke in China.

BACKGROUND AND AIM: Glycated albumin (GA) is a biomarker monitoring glycemia 2-4 weeks before stroke onset. This study was designed to explore the association between GA levels with poststroke outcomes in patients with acute ischemic stroke or transient ischemic attack (TIA). METHOD: Participants with ischemic stroke or TIA who had a baseline GA measurement were included in the Third China National Stroke Registry study. The effect of GA on stroke recurrence, poor functional outcomes, and combined vascular events was examined during the 1-year follow-up period. Multivariate Cox and logistic regression models were performed to evaluate the association. Discrimination tests were used to examine the incremental predictive value of GA when incorporating it into the conventional model. RESULTS: A total of 3861 participants were enrolled. At the 3-month follow-up, the elevated GA level was associated with an increased risk of poor functional outcomes (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.01-2.09). A similar increase was observed for stroke recurrence (adjusted hazard ratio [HR], 1.56; 95% CI, 1.09-2.24), poor functional outcomes (adjusted OR, 1.62; 95% CI, 1.07-2.45), and combined vascular events (adjusted HR, 1.55; 95% CI, 1.09-2.20) at the 1-year follow-up. In nondiabetic patients, the association between GA and poor functional outcomes was more pronounced (adjusted OR, 1.62; 95% CI, 1.05-2.50). Adding GA into the conventional model resulted in slight improvements in predicting poor functional outcomes (net reclassification improvement [NRI]: 12.30% at 1 year). CONCLUSION: This study demonstrated that elevated GA levels in serum were associated with stroke adverse outcomes, including stroke recurrence, poor functional outcomes, and combined vascular events, in patients with ischemic stroke or TIA.

Intelligent Supramolecular Modification for Implants: Endogenous Regulation of Bone Defect Repair in Osteoporosis.

Addressing osteoporosis-related bone defects, a supramolecular strategy is innovated for modifying carbon fiber reinforced polyether ether ketone (CF/PEEK) composites. By covalently attaching intelligent macromolecules via in situ RAFT polymerization, leveraging the unique pathological microenvironment in patients with iron-overloaded osteoporosis, intelligent supramolecular modified implant surface possesses multiple endogenous modulation capabilities. After implantation, surface brush-like macromolecules initially resist macrophage adhesion, thereby reducing the level of immune inflammation. Over time, the molecular chains undergo conformational changes due to Fe (III) mediated supramolecular self-assembly, transforming into mechanistic signals. These signals are then specifically transmitted to pre-osteoblast cell through the binding capacity of the KRSR short peptide at the molecular terminus, induced their osteogenic differentiation via the YAP/ß-catenin signaling axis. Furthermore, osteoblasts secrete alkaline phosphatase (ALP), which significantly hydrolyzes phosphate ester bonds in surface macromolecular side groups, resulting in the release of alendronate (ALN). This process further improves the local osteoporotic microenvironment. This intelligent surface modification tailors bone repair to individual conditions, automatically realize multiple endogenous regulation once implanted, and truly realize spontaneous activation of a series of responses conducive to bone repair in vivo. It is evidenced by improved bone regeneration in iron-overloaded osteoporotic rabbits and supported by in vitro validations.

Electrochemical aptasensor based on a dual signal amplification strategy of 1-AP-CNHs and ROP for highly sensitive detection of ERα.

Estrogen receptor alpha (ERα) serves as a crucial biomarker for early breast cancer diagnosis. In this study, we proposed an electrochemical aptasensor with nanomaterial carbon nanohorns/gold nanoparticle composites (1-AP-CNHs/AuNPs) as the substrate, and the primary amine groups on the antibody initiated the ring-opening polymerization (ROP) of monomer amino acid-ferrocene (NCA-Fc) on the electrode surface for ultrasensitive detection of ERα. The composite of 1-AP-CNHs/AuNPs not only possessed more active sites, but also increased the specific surface area of the electrode and allowed a large amount of ferrocene polymer long chains to be grafted onto the electrode surface to achieve signal amplification. Under optimal conditions, the detection limit of the method was 11.995 fg mL-1 with a detection range of 100 fg mL-1-100 ng mL-1. In addition, the biotin-streptavidin system was used to further improve the sensitivity of the sensor. Importantly, this approach could be applied for the practical detection of ERα in real samples.

Early vs Delayed Antihypertensive Treatment in Acute Single Subcortical Infarction: A Secondary Analysis of the CATIS-2 Randomized Clinical Trial.

Importance: The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) suggests that early antihypertensive treatment did not reduce the risk of dependency or death in acute ischemic stroke (AIS), compared with delayed treatment. Single subcortical infarction (SSI) is an important stroke subtype, and the association of antihypertensive timing with clinical outcomes is unclear. Objective: To investigate the association of early vs delayed antihypertensive treatment with clinical outcomes in patients with SSI, stratified by the presence of parent artery disease (PAD) stenosis. Design, Setting, and Participants: This secondary analysis of the CATIS-2 randomized clinical trial included 106 hospitals in China between June 2018 and July 2022. In CATIS-2, patients with AIS within 24 to 48 hours of symptoms onset and elevated systolic blood pressure were eligible. Patients with SSI detected in diffusion-weighted imaging were included in the current post hoc subgroup analysis. Patients were grouped into (1) SSI with PAD stenosis and (2) SSI without PAD stenosis. Statistical analysis was performed from July 2023 to May 2024. Exposures: Early (immediate) vs delayed (starting on day 8) antihypertensive therapy. Main Outcome and Measure: Primary outcome was the combination of functional dependency or death (modified Rankin Scale score ≥3) at 90 days. Results: Among 997 patients with SSI in CATIS-2 (mean [SD] age, 62.4 [9.8] years; 612 [61.4%] men), 116 (11.6%) had SSI with PAD and 881 (88.4%) had SSI without PAD. There was no significant difference in the primary outcome between early and delayed antihypertensive treatment groups among all patients with SSI (8.8% vs 7.1%; OR, 1.25 [95% CI, 0.79-1.99]; P = .34). Among patients with SSI with PAD, early antihypertensive treatment was associated with increased risk of the primary outcome compared with delayed treatment (23.4% vs 7.7%; OR, 3.67 [95% CI, 1.14-11.86]; P = .03); this finding was not observed in patients with SSI without PAD (6.6% vs 7.1%; OR, 0.93 [95% CI, 0.55-1.57]; P = .77). Significant interaction with treatment and presence of PAD stenosis was detected for the primary outcome (P for interaction = .04). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, early antihypertensive treatment was associated with an increased risk of functional dependency or death at 90 days among patients with SSI and coexisting PAD stenosis, compared with delayed antihypertensive treatment. Further studies are warranted for individualized BP management in patients with SSI by the presence of PAD. Trial Registration: ClinicalTrials.gov Identifier: NCT03479554.

Safety and efficacy of GD-11 in patients with ischaemic stroke: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

BACKGROUND: GD-11, a novel brain cytoprotective drug, was designed to be actively taken up and transported across the blood-brain barrier via the glucose transporter. This study aimed to evaluate the safety and efficacy of GD-11 for improving the recovery of patients with acute ischaemic stroke (AIS). METHODS: A double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 15 clinical sites in China. Patients aged 18-80 years with AIS within 48 hours were randomly assigned (1:1:1) to receive 160 mg GD-11, 80 mg GD-11 and placebo, two times a day for 10 days. The primary endpoint was a modified Rankin Scale (mRS) score of 0-1 at 90 days after treatment. The safety outcome was any adverse events within 90 days. RESULTS: From 17 November 2022 to 22 March 2023, a total of 80 patients in the 160 mg GD-11 group, 79 patients in the 80 mg GD-11 group and 80 patients in the placebo group were included. The proportion of an mRS score of 0-1 at day 90 was 77.5% in the 160 mg GD-11 group, 72.2% in the 80 mg GD-11 group and 67.5% in the placebo group. Though no significant difference was found (p=0.3671), a numerically higher proportion was observed in the GD-11 group, especially in the 160 mg GD-11 group. The incidence of adverse events was similar across the three groups (p=0.1992). CONCLUSION: GD-11 was safe and well-tolerated. A dosage of GD-11 160 mg two times a day was recommended for a large trial to investigate the efficacy.

Association between PPARγ polymorphisms and neurological functional disability of ischemic stroke.

Peroxisome proliferator-activated receptor-γ (PPARγ) plays a protective role against brain injury after stroke in mice. However, the relationship between PPARγ gene polymorphisms and the functional outcome of acute ischemic stroke (AIS) remains unknown. 8822 patients from The Third China National Stroke Registry (CNSR-III) after whole-genome sequencing, two functional single nucleotide polymorphisms(SNPs) in PPARγ, rs1801282 C > G and rs3856806 C > T, were further analysed. The primary outcome was neurological functional disability at three months. Of the 8822 patients, 968 (11.0%) and 3497 (39.6%) were carriers of rs1801282 and rs3856806, respectively. Carriers of rs3856806 showed reduced risks for three-month neurological functional disability (OR, 0.84; 95% CI, 0.73-0.98; p = 0.02) and reduced risks for higher infarct volume (OR 0.90, 95% CI, 0.81-0.99, p = 0.04). They also had a reduced risk of neurological functional disability only in case of lower baseline IL-6 levels (OR 0.64, 95% CI 0.48-0.84, Pinteraction = 0.01). Carriers of rs1801282 had a reduced risk for three-month neurological functional disability (OR 0.77, 95% CI, 0.61-0.99, p = 0.04). Our study suggested that PPARγ polymorphisms are associated with a reduced risk for neurological functional disability and higher infarct volume in AIS. Therefore, PPARγ can be a potential therapeutic target in AIS.

Progresses and Perspectives of Carbon-Free Metal Compounds-Modified Separators for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) have the advantages of high theoretical specific capacity, excellent energy density, abundant elemental sulfur reserves. However, the LSBs is mainly limited by shuttling of lithium polysulfides (LiPSs), slow reaction kinetics of sulfur cathode. For solving the above problems, by developing high-performance battery separators, the reversible capacity, Coulombic efficiency (CE) and cycle life of LSBs can be effectively enhanced. Carbon-free based metal compounds are expected to be highly efficient separator modifiers for a new generation of high-performance LSBs by virtue of superior chemical adsorption capacity, strong catalytic properties and excellent lithophilicity to a certain extent. They can give play to the synergistic effect of their "adsorption-catalysis" sites to accelerate the redox kinetics of LiPSs, and their good lithophilicity can accelerate the Li+ transport kinetics, thus showing more remarkable electrochemical performances. However, a comprehensive summary of carbon-free metal compounds-modified separators for LSBs is still lacking. Here, this review systematically summarizes the researching progresses and performance characteristics of carbon-free-based metal compounds modified materials for separators of LSBs, and summarizes the corresponding mechanisms of using carbon-based separators to enhance the performance of LSBs. Finally, the review also looks forward to the prospects of LSBs using carbon-free metal compounds separators.

Association and temporal sequence of pneumonia and gastrointestinal bleeding after acute ischemic stroke.

BACKGROUND: Stroke-associated pneumonia (SAP) and gastrointestinal bleeding (GIB) are common medical complications after stroke. The previous study suggested a strong association between SAP and GIB after stroke. However, little is known about the time sequence of SAP and GIB. In the present study, we aimed to verify the association and clarify the temporal sequence of SAP and GIB after ischemic stroke. METHODS: Patients with ischemic stroke from in-hospital Medical Complication after Acute Stroke study were analyzed. Data on occurrences of SAP and GIB during hospitalization and the intervals from stroke onset to diagnosis of SAP and GIB were collected. Multiple logistic regression was used to evaluate the association between SAP and GIB. Kruskal-Wallis test was used to compare the time intervals from stroke onset to diagnosis of SAP and GIB. RESULTS: A total of 1129 patients with ischemic stroke were included. The median length of hospitalization was 14 days. Overall, 86 patients (7.6%; 95% CI, 6.1-9.2%) developed SAP and 47 patients (4.3%; 95% CI, 3.0-5.3%) developed GIB during hospitalization. After adjusting potential confounders, SAP was significantly associated with the development of GIB after ischemic stroke (OR = 5.13; 95% CI, 2.02-13.00; P < 0.001). The median time from stroke onset to diagnosis of SAP was shorter than that of GIB after ischemic stroke (4 days vs. 5 days; P = 0.039). CONCLUSIONS: SAP was associated with GIB after ischemic stroke, and the onset time of SAP was earlier than that of GIB. It is imperative to take precautions to prevent GIB in stroke patients with SAP.