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Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment.

BackgroundEndovascular treatment (EVT) is a well-established approach for acute ischemic stroke. Whether bridging intravenous thrombolysis (IVT) before EVT confers any benefits remains uncertain. The objective of the study was to compare the efficacy and safety of direct EVT with or without bridging IVT in patients with acute basilar artery occlusion (BAO).MethodsThis multicenter cohort study enrolled 647 patients with acute BAO who underwent either bridging IVT before EVT or direct EVT from the BASILAR registry. The primary outcome was an independent functional outcome measured by the modified Rankin Scale (mRS) score of 0–2. Secondary outcomes included excellent functional outcome (mRS 0–1), favorable functional outcome (mRS 0–3), and mortality rate at 90 days, as well as symptomatic intracranial hemorrhage (sICH), and successful reperfusion between the two treatment groups.ResultsDirect EVT and bridging IVT before EVT exhibited similar primary outcomes (27.3% vs 27.7%, respectively) and distributions of mRS scores at 90 days. Moreover, rates of sICH and 90-day mortality were not significantly different between the two groups (7.3% vs 6.0%, adjusted OR (aOR) 0.79, 95% CI 0.34 to 1.86, P=0.84 for sICH; 46.8% vs 43.7%, aOR 0.86, 95% CI 0.54 to 1.38, P=0.53 for mortality).ConclusionsAmong patients with acute BAO, functional outcomes were similar between those treated with bridging IVT before EVT and those treated with direct EVT, and there was no difference between the two groups in terms of sICH and mortality rates.

ObjectiveTo evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups.MethodsWe pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0–2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality.ResultsWe included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable.ConclusionsThe cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.

BackgroundPredicting mortality in stroke patients using information available before endovascular treatment (EVT) is an essential component for supporting clinical decision-making. Although the mortality rate of acute basilar artery occlusion (ABAO) after EVT has reached 40%, few studies have focused on predicting mortality in these individuals. Thus, we aimed to develop and validate a machine learning-based mortality prediction tool based on preoperative information for ABAO patients receiving EVT.MethodsThe derivation cohort comprised patients from southern provinces of China in the BASILAR registry. The model (POSITIVE: Predicting mOrtality of baSilar artery occlusion patIents Treated wIth EVT) was trained and optimized using a fivefold cross-validation method in which hyperparameters were selected and fine-tuned. This model was retrospectively tested in patients from the northern provinces of China from the BASILAR registry. A prospective test of POSITIVE was performed on consecutive patients from two hospitals between January 2020 and June 2022.ResultsExtreme gradient boosting was employed to construct the POSITIVE model, which achieved the best predictive performance among the eight machine learning algorithms and showed excellent discrimination (area under the curve (AUC) 0.83, 95% confidence interval (95% CI) 0.80 to 0.87) and calibration (Hosmer-Lemeshow test, P>0.05) in the development cohort. AUC yielded by the POSITIVE model for the retrospective test was 0.79 (95% CI 0.71 to 0.85), higher than that obtained by traditional models. Prospective comparisons showed that the POSITIVE model achieved the highest AUC (0.82, 95% CI 0.74 to 0.90) among all prediction models.ConclusionWe developed a machine learning algorithm and retrospective and prospective testing with multicentric cohorts, which exhibited a solid predictive performance and may act as a convenient reference to guide decision-making for ABAO patients. The POSITIVE model is presented online for user-friendly access.

Talarolactones A–G (1–7), seven novel α-pyrone adducts with unprecedented scaffolds, together with two pairs of α-pyrone monomers [(±)-8and (±)-9)] were isolated from Talaromyces adpressus. Compounds 1–7are highly modified α-pyrone dimers with a 4,7,7,8-tetrasubstitued 5,6,7,8-tetrahydro-2H-chromen-2-one. Compounds 5and 6possessed a significant NO production inhibitory effect, with IC50values of 2.3 ± 0.1 and 3.7 ± 0.3 μM, respectively. Plausible biosynthetic pathways were proposed and supported by the results of heterologous expression experiments.

BackgroundThe effects of secondary collateral compensation on outcomes remain unclear in patients with acute basilar artery occlusion (BAO) after endovascular treatment (EVT). This study aimed to evaluate the benefits of the anastomosis between the posterior inferior cerebellar artery (PICA) and the superior cerebellar artery (SCA) in BAO after EVT.MethodsThis cohort study was conducted using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry. Patients with acute BAO and treated with EVT were included. The primary outcome was a modified Rankin Scale score of 0–2 at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (SICH) and 90-day mortality.ResultsOf the 646 patients included in the study, 196 (30.3%) patients had a PICA–SCA anastomosis. The PICA–SCA anastomosis was significantly associated with independent functional outcome at 90 days (67/196 (34.2%) vs 109/450 (24.2%), adjusted OR (aOR) 1.80 (95% CI 1.13 to 2.86), p=0.01) and was significantly associated with a decreased rate of SICH (40/442 (9.0%) vs 5/193 (2.6%), aOR 0.29 (95% CI 0.11 to 0.76), p=0.01). No significant difference was found between PICA–SCA anastomosis and 90-day mortality (219/450 (48.7%) vs 80/196 (40.8%), aOR 0.72 (95% CI 0.48 to 1.08), p=0.11). Subgroup analysis showed that the association between independent functional outcome and PICA–SCA anastomosis was strongest in patients with middle BAO (27/77 (35.1%) vs 22/118 (18.6%), aOR 2.64 (95% CI 1.13 to 6.15), p=0.03).ConclusionsThe PICA–SCA anastomosis is significantly associated with better functional outcomes in patients with acute BAO after EVT, especially in those with middle BAO.

BackgroundLocked-in syndrome (LiS) is a rare and devastating condition in patients with acute basilar artery occlusion. However, the benefits of endovascular treatment (EVT) for LiS remain unclear.ObjectiveTo assess the outcomes associated with EVT and identify the factors associated with outcomes of LiS.MethodsWe used the data of the Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry (BASILAR) from 47 tertiary stroke centers in China. The included patients had LiS and received EVT or standard medical treatment (SMT) alone. The primary outcome was improvement in the modified Rankin Scale (mRS) score at 90 days.ResultsAmong the 120 patients with LiS, 92 (76.7%) received EVT and 28 (23.3%) received SMT. Compared with SMT, EVT was associated with improved mRS score (common OR (cOR)=2.68 (95% CI 1.16 to 6.20); p=0.02) and decreased mortality (aOR=0.35 (95% CI 0.13 to 0.90); p=0.03). Moreover, the benefit of EVT for LiS was sustained for at least 1 year (p=0.008). Higher baseline posterior circulation Alberta Stroke Prognosis Early CT Score (pc-ASPECTS, aOR=2.04 (95% CI 1.34 to 3.10); p<0.001) and absence of pneumonia (aOR=0.26 (95% CI 0.08 to 0.90); p=0.03) were significantly associated with favorable functional outcome at 90 days in patients who received EVT, while lower pc-ASPECTS (aOR=0.52 (95% CI 0.36 to 0.76); p<0.001) was associated with increased 90-day mortality.ConclusionsThis study found that EVT was associated with favorable functional outcomes and decreased mortality among patients with LiS. Baseline pc-ASPECTS and pneumonia were independent predictors of outcomes.

BackgroundHigher extended Thrombolysis In Cerebral Infarction (eTICI) grades are associated with better clinical outcomes after endovascular treatment (EVT) for proximal intracranial occlusion of the anterior circulation. However, the relationship between eTICI grade and outcomes after EVT in patients with acute basilar artery occlusion (BAO) remains unclear. We aimed to explore which eTICI category was the cut-off correlating with better clinical outcomes in patients with BAO undergoing EVT.MethodsWe included patients treated via EVT from the BASILAR study. Multivariable logistic regression analyses were performed to assess the impact of eTICI grades on 90-day favorable functional outcomes, defined as a modified Rankin Scale (mRS) score of 0–3. Other outcomes were functional independence (mRS 0–2), all-cause mortality, and symptomatic intracranial hemorrhage.ResultsAmong 647 patients treated with EVT, 127 (19.6%), 128 (24.5%), 110 (21.1%), and 282 (54%) patients achieved eTICI grades of 0–2a, 2b, 2c, and 3, respectively. Compared with eTICI grades 0–2a, higher rates of favorable functional outcomes (adjusted OR (aOR) 2.96, 95% CI 1.33 to 6.57, and aOR 7.40, 95% CI 3.63 to 15.09, respectively) were observed for grades 2c and 3, not 2b (aOR 1.93, 95% CI 0.86 to 4.36). The risks of mortality and symptomatic intracranial hemorrhage were also lower for eTICI grades 2c and 3 than for grades 0–2a.ConclusionsAn eTICI grade of 2c/3 may be a target for successful reperfusion after EVT in patients with acute BAO; however, further studies with larger sample sizes and clinical trials are needed.

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SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.

BackgroundThe best anesthetic management strategy for patients with acute large vessel occlusion treated with mechanical thrombectomy (MT) remains uncertain. Most studies have focused on anterior–circulation stroke caused by large artery occlusion. Nevertheless, limited data are available on the appropriate choice of anesthetic for acute basilar artery occlusion (BAO). We aimed to investigate the effect of anesthetic method on clinical outcomes in patients with BAO undergoing MT.MethodsPatients undergoing MT for acute BAO in the BASILAR registry (Acute Basilar Artery Occlusion Study) were included. We divided patients into three groups according to the anesthetic technique used during MT: general anesthesia (GA), local anesthesia (LA), and conscious sedation (CS). Propensity score matching was performed to achieve baseline balance.Results639 patients were included. GA was used in 257 patients (40.2%), LA was used in 250 patients (39.1%), and CS was used in 132 patients (20.7%). After 1:1 matching, favorable outcome, mortality, and hemorrhagic transformation rates, as well as modified Rankin Scale (mRS) score at 90 days, did not differ between the GA, LA, and CS groups.ConclusionsThe choice of anesthetic strategy, GA, LA, or CS, did not affect the clinical outcomes of patients with acute BAO treated with MT in the BASILAR registry.

We reported the characterization of a novel brassicicene diterpene biosynthetic gene cluster, which contains a unique α-ketoglutarate-dependent dioxygenase (αKGD) enzyme, AbnI. Our findings revealed that AbnI demonstrates remarkable substrate promiscuity and is capable of activating multiple sites on both 5–8–5 and 5–9–5 brassicicene skeletons, resulting in skeleton modifications and an unexpected ring system rearrangement. These results suggested the potential utility of AbnI as an enzymatic tool for terpene CH functionalization. In addition, the catalytic mechanism of AbnI and its potential ecological implications were discussed.

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The well-developed tectonically deformed coals (TDCs) and the high heterogeneity of coalbed methane (CBM) occurrence severely restrict the sustainable development of the CBM industry in structurally complex areas. To better understand micro- and mesopore structures (0–50 nm) of TDCs and their influence on methane adsorption properties, we conducted methane adsorption tests and multifractal characterization (based on N2and CO2gas adsorption tests) on samples with different degrees of brittle deformation. Multifractal analyses indicate that the pore volume (PV) and pore surface area (PSA) distributions of micro- and mesopores have multifractal characteristics. The multifractal dimensions can be used to quantitatively characterize the heterogeneity and continuity of PV and PSA distributions. Correlation analyses demonstrated that the multifractal properties of the PV and PSA distributions of micro- and mesopores are significantly influenced by pore structure changes related to coal deformation. Interestingly, the multifractal dimensions of pore size distributions (both the PV and PSA distributions, particularly 1–10 nm pores) have significant negative correlations with the methane adsorption properties of coal, indicating that a uniform pore size distribution is favorable for a high maximum methane adsorption capacity. The increase in 1–10 nm pore occurrence due to tectonic activity also enhanced the adsorption capacity of strongly deformed coals. The influences of coal deformation on the methane adsorption capacity of coal could be attributed to two aspects: increase in the PV and PSA of 1–10 nm pores and decrease in heterogeneity differences of pore size distributions. These two effects result in a higher gas content and pressure in the distribution areas of strongly deformed coals, which lead to higher risks of gas-related disasters.

Bioassay-directed isolation of secondary metabolites from an extract of Penicillium chrysogenumTJ403-CA4 isolated from the medicinally valuable arthropod Cryptotympana atrataafforded five new and 10 known compounds (1–15). All the compounds (except 14) belong to a minor class of highly rigid 6–5–5–5-fused tetracyclic cyclopiane-type diterpenes known to be exclusively produced by members of the Penicilliumgenus. The structures and absolute configurations of the new compounds (1–5) were elucidated by extensive spectroscopic analyses, including HRESIMS and 1D and 2D NMR, single-crystal X-ray diffraction, and comparison of the experimental electronic circular dichroism data. Compounds 1and 2represent the first examples of cyclopianes bearing a C-20 carboxyl group; compound 3represents the first example of a cyclopiane with a gem-hydroxymethyl group; compound 4represents the second example of a cyclopiane bearing a hydroxy group at C-7; compound 5represents the first example of a cyclopiane bearing a hydroxy group at C-8. Compounds 2and 3exhibited activity against MRSA, with MIC values of 4.0 and 2.0 μg/mL, respectively. In addition, the structure–antibacterial activity relationship (SAR) of compounds 1–15is discussed.

Seven new modified fusicoccane-type diterpenoids (1–7), together with two known congeners (8and 9), were obtained from Alternaria brassicicola. Their structures were elucidated from a combination of NMR and HRESIMS data and 13C NMR calculation as well as DP4+ probability analyses, and the absolute configurations of 1–5were determined by ECD calculation and single-crystal X-ray diffraction (Cu Kα). Compounds 1–3belong to a rare class of 16-nor-dicyclopenta[a,d]cyclooctane diterpenoids, and compounds 2and 4represent the first examples of fusicoccane-type diterpenoids featuring two previously undescribed tetracyclic 5/6/6/5 ring systems, while compound 5features a previously undescribed tetracyclic 5/8/5/3 ring system. Compound 7was moderately anti-inflammatory, and compounds 2, 3, 5, and 7were weakly cytotoxic.

IMPORTANCE: Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. OBJECTIVE: To evaluate the association between EVT and clinical outcomes of patients with acute BAO. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. MAIN OUTCOMES AND MEASURES: The primary outcome was the improvement in modified Rankin Scale scores (range, 0 to 6 points, with higher scores indicating greater disability) at 90 days across the 2 groups assessed as a common odds ratio using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as modified Rankin Scale scores of 3 or less (indicating an ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage and 90-day mortality. RESULTS: A total of 1254 patients were assessed, and 829 patients (of whom 612 were men [73.8%]; median [interquartile] age, 65 [57-74] years) were recruited into the study. Of these, 647 were treated with standard medical treatment plus EVT and 182 with standard medical treatment alone. Ninety-day functional outcomes were substantially improved by EVT (adjusted common odds ratio, 3.08 [95% CI, 2.09-4.55]; P &lt; .001). Moreover, EVT was associated with a significantly higher rate of 90-day modified Rankin Scale scores of 3 or less (adjusted odds ratio, 4.70 [95% CI, 2.53-8.75]; P &lt; .001) and a lower rate of 90-day mortality (adjusted odds ratio, 2.93 [95% CI, 1.95-4.40]; P &lt; .001) despite an increase in symptomatic intracerebral hemorrhage (45 of 636 patients [7.1%] vs 1 of 182 patients [0.5%]; P &lt; .001). CONCLUSIONS AND RELEVANCE: Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality.

The reported fumiquinazoline-related alkaloids cottoquinazolines E–G (1–3) were reisolated from solid cultures of the fungus Neosartorya fischeri, which was isolated from the medicinal arthropod Cryptotympana atrata. The unresolved issues regarding the absolute configurations (for cottoquinazolines E and F) prompted a reinvestigation of the configurations for all three compounds, as enabled by extensive spectroscopic methods, comparisons of experimental electronic circular dichroism data, and X-ray crystallography. In addition, cottoquinazoline F (2) showed significant antibacterial activity against ESBL-producing Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecaliswith MIC values of 8, 32, 32, and 16 μg/mL, respectively.

Three new rare cyclopiane diterpenes (1–3) and thirteen known compounds (4–16) were isolated from a sea sediment-derived fungus Penicilliumsp. TJ403-2. The absolute structures of 1–3were confirmed by X-ray crystallography experiment and the anti-inflammatory activity against LPS-induced NO production was also evaluated.

TlnA produces a distinct cyclohexane-fused 5–8–6 ring system, different from the prevalent 5–8–5 scaffold synthesized by well-established enzymes. This study identifies two conformations of a carbocation intermediate, revealing how the enzyme environment prohibits one conformation due to steric hindrance, thereby directing the formation of the 5–8–6 system over the 5–8–5 scaffold. This investigation enhances our understanding of diterpene biosynthesis and the impact of enzyme environments on chemical reactions, providing valuable insights into the formation of complex cyclic structures.

Background and Purpose Two early basilar artery occlusion (BAO) randomized controlled trials (RCTs) did not establish the superiority of endovascular thrombectomy (EVT) over medical management. Yet many providers continued to recommend EVT. The goal of the present article is to compare physicians’ diagnostic and management strategies of BAO among middle-income and high-income countries (MICs and HICs, respectively).Methods We conducted an international survey from January to March 2022 regarding management strategies in acute BAO, to examine clinical and imaging parameters influencing clinician management of patients with BAO. We compared responses between physicians from HIC and MIC.Results Among the 1245 respondents from 73 countries, 799 (64.2%) were from HIC, with the remaining 393 (31.6%) from MIC. Most respondents perceived that EVT was superior to medical management for acute BAO, but more so in respondents from HIC (98.0% vs. 94.2%, p < 0.01). MIC respondents were more likely to believe further RCTs were warranted (91.6% vs. 74.0%, p < 0.01) and were more likely to find it acceptable to enroll any patient who met a trial’s criteria in the standard medical treatment arm (58.8% vs. 38.5%, p < 0.01).Conclusions In an area where clinical equipoise was called into question despite the lack of RCT evidence, we found that respondents from MIC were more likely to express willingness to enroll patients with BAO in an RCT than their HIC counterparts.

Background The superiority of endovascular thrombectomy (EVT) over medical management was not established in two early basilar artery occlusion (BAO) randomized controlled trials. Despite this, many clinicians recommended EVT for acute BAO under certain circumstances. This paper aims to compare physicians’ diagnostic and management strategies of BAO according to gender.Methods From January to March 2022 an international survey was conducted regarding management strategies in acute BAO. We compared responses between clinicians by identifying gender. Questions were designed to examine clinical and imaging parameters influencing management of patients with BAO.Results Among the 1245 respondents from 73 countries, 311 (25.0%) identified as female. This figure was 13.6% amongst interventionists. Geographically, female respondents were lowest in Asia (14.5%) and North America (23.9%). The proportion of respondents identifying as female was consistent regardless of their years of experience. Female respondents were more likely to choose time of onset as time of first estimated stroke like symptom (48.0% vs. 38.5%, p< .01), were less likely to favor thrombectomy in the V4 segment of vertebrobasilar artery occlusions (31.5% vs. 43.3%, p< .01), and were less likely to find it acceptable to enroll all patients who met trial criteria in the standard medical treatment arm of a clinical trial (41.2% vs. 47.0%, p= .01). Male respondents were more likely to agree that thrombolysis would not alter their decision on proceeding with EVT (93.7% vs. 88.3%, p< .01).Conclusions Female clinicians appear to be significantly underrepresented in stroke medicine. This is most pronounced amongst interventionists and in Asia. Although male and female opinions were closely aligned on many aspects of BAO management, differences in opinion were observed in a number of significant areas which influence decision making.

Background and purpose: The efficacy and safety of tirofiban in endovascular therapy for cardioembolic ischemic stroke patients remain controversial. This study aimed to evaluate the role of intravenous tirofiban before endovascular therapy in cardioembolic stroke. Methods: This post hoc analysis utilized data from the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke) trial, which was an investigator-initiated, randomized, double-blind, placebo-controlled trial. Participants were randomized to receive either tirofiban or a placebo in a 1:1 ratio before undergoing endovascular therapy. The study included patients aged 18 years or older, presenting with occlusion of the internal carotid artery or middle cerebral artery (MCA) M1/M2 within 24 h of the last known well time, and with a stroke etiology of cardioembolism. The primary efficacy outcome was global disability at 90 days, assessed using the modified Rankin Scale (mRS). The safety outcome included symptomatic intracranial hemorrhage (sICH) within 48 h and mortality within 90 days. Results: A total of 406 cardioembolic stroke patients were included in this study, with 212 assigned to the tirofiban group and 194 assigned to the placebo group. Tirofiban treatment did not correlate with a favorable shift towards a lower 90-day mRS score (adjusted common odds ratio [OR], 0.91; 95% CI 0.64–1.3; p= 0.617). However, the tirofiban group had a significantly higher risk of symptomatic intracranial hemorrhage (sICH) within 48 h (adjusted OR, 3.26; 95% CI 1.4–7.57; p= 0.006) compared to the placebo group. The adjusted odds ratio (aOR) for mortality within 90 days was 1.48 (95% CI 0.88–2.52; p= 0.143). Conclusions: Tirofiban treatment was not associated with a lower level of disability and increased the incidence of sICH after endovascular therapy in cardioembolic stroke patients.

Graphical Abstract:

Alterbrassinoids A–D (1–4), the first examples of fusicoccane-derived diterpenoid dimers furnished by forming an undescribed C-12–C-18′ linkage, were isolated from modified cultures of Alternaria brassicicola. Compounds 1and 2represent unprecedented heterodimers, whereas 3and 4represent unprecedented homodimers, and 4also features an undescribed anhydride motif. Their structures were assigned via spectroscopic methods, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Putative biosynthetic pathways and a bioactivity evaluation for 1–4were discussed.

Periconiastone A (1), an ergosterol with an unprecedented pentacyclo[8.7.0.01,5.02,14.010,15]heptadecane system, was isolated from Periconiasp. TJ403-rc01. Its structure was assigned by extensive spectroscopic analyses and quantum-chemical 13C NMR and ECD calculations. A vinylogous α-ketol rearrangement and an aldol condensation reaction during biosynthesis were proposed as key steps for the formation of 1. Compound 1showed antibacterial activity against Gram-positive S. aureusand E. faecaliswith MIC values of 4 and 32 μg/mL, respectively.

An HPLC-DAD-directed chemical investigation of the soil-derived fungus Aspergillus versicolorQC812 resulted in the isolation and identification of eight new linearly fused prenylated indole alkaloids, asperversiamides I–P (1–8), along with a congener, asperversiamide H (9). Their structures and absolute configurations were determined by spectroscopic analysis including HRESIMS and 1D and 2D NMR, electronic circular dichroism analysis, and single-crystal X-ray diffraction. Asperversiamide I (1), the first diketopiperazine derived from d-proline and l-tryptophan, possesses an unprecedented C-11-spiro-fused 6/6/5/5/6/5 hexacyclic ring system. Asperversiamide J (2) is the first linearly fused 6/6/5 tricyclic prenylated indole alkaloid to be reported. 1and 2showed moderate inhibitory activities against HeLa cells with IC50values of 7.3 and 6.4 μM, respectively.

Alterbrassicicene A (1), a fusicoccane-derived diterpenoid with an unprecedented framework, together with two known biosynthetic intermediates (2and 3), were characterized from Alternaria brassicicola. The absolute structure of 1was assigned by extensive spectroscopic analyses and quantum chemical calculations. Compound 1represents a newly transformed monocyclic carbon skeleton of a highly functionalized diterpenoid bearing unique dihydro-2(3H)-furanone and 2-cyclopenten-1-one motifs. Compound 1was the first fusicoccane-derived diterpenoid functioning as a potent PPAR-γ agonist (EC50= 744.1 nM).

PurposeTo evaluate the effectiveness and safety of rescue stenting (RS) after failed mechanical thrombectomy (MT) for patients with large artery occlusion in the anterior circulation.MethodsConsecutive patients who experienced failed reperfusion and subsequently did or did not undergo RS at 16 comprehensive stroke centers were enrolled from January 2015 to June 2018. Propensity score matching was used to achieve baseline balance between the patient groups. Symptomatic intracranial hemorrhage (sICH) at 48 hours and the modified Rankin Scale scores and mortality at 3 months in the two groups were compared.ResultsA total of 90 patients with RS and 117 patients without RS after failed MT were enrolled. Propensity score matching analysis selected 132 matched patients. The good outcome rate was significantly higher in matched patients with RS than in those without RS (36.4% vs 19.7%, p=0.033), whereas the sICH (13.6% vs 21.2%, p=0.251) and mortality (31.9% vs 43.9%, p=0.151) were not significantly different between the groups.ConclusionsRS seems to be an effective safe choice for patients with large vessel occlusion of the anterior circulation who underwent failed MT.

The structure–stability relationships of 1–6were investigated to show that 1converted to 5via a kinetic, solution-mediated autoxidation. In addition, alterbrassicene A (7), a fusicoccane-derived diterpenoid bearing an unprecedented 5/9/4-fused carbocyclic skeleton with a rare fused 2-cyclobuten-1-one motif, was characterized from Alternaria brassicicola. Its absolute structure was elucidated by spectroscopic analyses and quantum chemical calculations. Compound 7was the first fusicoccane derivative acting as a potent IKKβ inhibitor in the NF-κB signaling pathway.

BackgroundElevated mean platelet volume (MPV), indicating higher platelet activity, could be a predictor of prognosis in patients with acute ischemic stroke receiving medical therapy.ObjectiveTo investigate the relationship between MPV and functional outcome in patients with acute anterior circulation stroke 3 months after undergoing mechanical thrombectomy (MT).MethodsA total of 153 consecutive patients with acute stroke following MT, in two separate stroke centers, were enrolled between May 2013 and March 2016. MPV was measured on admission. Subjects were divided into two groups according to average MPV level. Univariate and multivariate analyses were performed. MPV was also incorporated into the Houston IA Therapy (HIAT) score, which was developed as a scoring system to predict poor prognosis, and the prediction capability was compared with the HIAT score alone.ResultsThe average MPV was 10.4 fL. Patients with high MPV had a significantly lower rate of functional independence (28.9% vs 57.1%, p=0.000). After multivariable analysis, elevated MPV remained an independent predictor of unfavorable outcome (OR=3.93, 95% CI 1.73 to 8.94, p=0.001). When the MPV cut-off value was set at 10.4 fL using the receiver operating characteristic (ROC) analysis, MPV ≥10.4 fL predicted unfavorable outcome with 62.1% sensitivity and 66.7% specificity, respectively. Addition of MPV to the HIAT score did not improve predictive power compared with the HIAT score system alone by a comparison of the areas under the two ROC curves (0.70 vs 0.62, p=0.174).ConclusionsElevated MPV is an independent predictor of poor outcome in patients with acute anterior circulation stroke undergoing MT at 3 months.

Background:The efficacy and safety of tirofiban, as an adjuvant medication of endovascular therapy (EVT), in patients with large vessel occlusion due to atherosclerotic thrombosis was still unclear.Methods:The Endovascular Treatment With versus Without Tirofiban in Stroke (RESCUE BT) trial was a randomized, double-blinded, placebo-controlled trial that was performed at 55 centers in China from October 10, 2018 to October 31, 2021. This was a post hoc exploratory analysis of the RESCUE BT trial and 435 patients were included in the intention-to-treat analysis. The primary outcome was the proportion of functional independence (defined as modified Rankin Scale 0-2) at 90 days. We estimated the efficacy and safety of EVT plus placebo versus EVT plus tirofiban using binary logistic regression analysis. A causal mediation analysis was also performed to assess the potential mediators of tirofiban on functional outcome.Results:This study included 435 patients, including 197 patients assigned to the tirofiban group and 238 patients assigned to the placebo group. The median age was 65 [IQR, 56-72] years, and 311 (71.5%) patients were men. Tirofiban was associated with higher rates of functional independence at 90 days compared with the placebo (adjusted odds ratio with 95% CI, 1.68 [1.11–2.56], P= 0.014). There was no significant difference in mortality and symptomatic intracranial hemorrhage between the two groups, thought the rate of intracranial hemorrhage was numerically higher in the tirofiban group (29.1% versus 23.2%, P= 0.165). Tirofiban was also associated with fewer number of thrombectomy passes (beta, -0.48; 95% CI, -0.62 to -0.34; P< 0.001). Treatment-reduced passes explains 20.0% (95% CI, 4-76) of the beneficial effect of tirofiban on functional independence.Conclusion:Tirofiban plus EVT might be an effective and well-tolerated option for patients with anterior large vessel occlusion due to atherosclerosis. These findings are needed to be confirmed in future trials.

Background:First-pass effect (FPE) defined as a complete or near-complete reperfusion achieved after a single thrombectomy pass is predictive of favorable outcome in acute ischemic stroke (AIS) patients with large vessel occlusion. It remains uncertain whether intravenous tirofiban is effective to improve the rate of FPE in anterior circulation strokes.Methods:RESCUE-BT (A randomized controlled trial of intravenous tirofiban or placebo prior to endovascular thrombectomy for large vessel occlusion stroke) enrolled 948 patients with proximal intracranial large vessel occlusion presenting within 24 hours of time last known well to receive intravenous either tirofiban or placebo before endovascular thrombectomy. Patients who did not treated with endovascular thrombectomy were excluded from this cohort. The endpoint was FPE, which defined by extended thrombolysis in cerebral infarction (eTICI) scale 2b, 2c or 3 after the first pass. A modified Poisson regression analysis was performed to assess the association between intravenous tirofiban treatment and FPE.Results:Twenty-two patients were excluded for not treating with endovascular thrombectomy. The remaining 926 patients were included (mean age, 66 years; 380 [41.0%] women), with 450 in the tirofiban and 476 in the placebo group, respectively. Among them, an FPE was achieved in 141 patients (31.3%) of the tirofiban group vs 114 patients (23.9%) of the placebo group. The adjusted risk ratio for FPE with tirofiban vs placebo was 1.24 (95%CI, 1.02-1.52).Conclusions:Treatment with intravenous tirofiban before endovascular thrombectomy significantly increased the incidence of FPE in acute ischemic stroke patients with large vessel occlusion presenting within 24 hours of time last known well.

Background and Objectives:Previous studies have shown the impact of procedure time (PT) on large vessel occlusion (LVO), however, the relationship for patients with acute basilar artery occlusion (ABAO) was not clear. We aimed to characterize the impact of PT and other procedure-related variables on clinical outcomes among patients with ABAO that underwent mechanical thrombectomy (MT).Methods:Patients with ABAO that underwent MT with a documented PT in the BASILAR study from January 2014 to May 2019 among 47 comprehensive centers in China were included. Multivariable analysis was performed to reveal the association between PT and 90-day modified Rankin Scale score, mortality, complications, and all-cause death at one year.Results:Of the 829 patients from the BASILAR registry, 633 eligible patients were included. A decreased likelihood of favorable outcomes (defined as a modified Rankin Scale score of 0-3 at 90 days) was demonstrated when PT exceeded 60 min (P < 0.001). Additionally, a PT ≤ 75 min independently predicted favorable outcomes (adjusted OR 2.28[95% CI 1.41- 3.68], respectively). The risk of complications and mortality increased by 0.5% and 1.5% with every 10 min increase in PT, respectively (R2= 0.64 and R2= 0.68, P <0.01). The cumulative rates of favorable outcomes and successful recanalization plateaued after 120 min (2 attempts). Restricted cubic spline regression analysis for the probability of favorable outcomes had an L-shape association (P non-linearity = 0.048) with PT with significant benefit loss before 120 min and then appeared relatively flat.Discussion:For ABAO patients, procedures that exceeded 75 min increased the risk of mortality and decreased the likelihood of a favorable outcome. For procedures exceeding 120 min the benefits and costs of continuing the procedure should be carefully considered.Classification of Evidence:This study provides Class II evidence for ABAO patients undergoing EVT.

Background:Two early basilar artery occlusion (BAO) randomized controlled trials did not establish superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to medical management may differ between clinician specialties.Methods:We conducted an international survey (1/1/22-3/31/22) regarding management strategies in acute BAO prior to the announcement of 2 trials indicating superiority of EVT, and compared responses between interventionalists (INT) and non-interventionalists (nINT). Selection practices for routine EVT based on neuroimaging and clinical features were compared between the two groups using descriptive statistics.Results:Among the 1245 respondents (nINT=702), INT more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p<0.01). A similar proportion of INT and nINT responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific circumstances (p=0.45). Among respondents who would recommend EVT, there was no difference in the maximum pre-stroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p>0.05), although nINT more commonly preferred perfusion imaging (24.2% vs. 19.7%, p=0.04). Among respondents who indicated they would randomize to medical management, INT were more likely to randomize when the NIHSS was ≥10 (15.9% vs. 6.9%, p<0.01).Conclusions:Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a patient to medical treatment. There were small differences in preference of advanced neuroimaging, although these preferences were unsupported by clinical trial data.

Background:In the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Stroke Patients with Large Vessel Occlusion) trial, enrollment in extended time window was based on non-contrast computed tomography. To assess whether tirofiban was safe and effective in the RESCUE BT trial according to advance imaging selection criteria based on current American Heart Association guidelines.Methods:This is a secondary analysis of a multicenter, double-blinded and randomized trial that was conducted at 55 centers in China and involved 950 participants with stroke with large vessel anterior circulation occlusion from October 2018 to October 2021. All randomized patients were screened according to the current guidelines and were followed up for 90 days from stroke onset. The primary outcome was the distribution of the 90-day modified Rankin scale (mRS) scores. Secondary outcomes included the rates of functional independence (mRS 0-2) and favorable outcome (mRS 0-3). Safety outcomes included the incidences of symptomatic intracranial hemorrhage (sICH) within 48 hours and 90-day mortality.Results:A total of 652 patients (319 in tirofiban group and 333 in placebo group) who met the current guidelines were included in this analysis, with median (IQR) age of 68 (58-75) years, 278 (42.6%) were women. The median 90-day mRS score was 3 (IQR, 1-4) in tirofiban group, and 3 (IQR, 1-4) in placebo group. The adjusted common odds ratio (OR) for a lower level of disability with tirofiban than placebo was 1.08 (95% confidence intervals [CI] 0.83-1.42). Incidence of sICH (10.1% vs6.3%; adjusted OR 1.70 [95%CI 0.95-3.04]) was not different between groups. However, intravenous tirofiban might be associated with lower disability level (adjusted common OR 1.74 [95%CI 1.14-2.65]; P=0.01) in large artery atherosclerosis patients.Conclusions:There was no significant difference in severity of disability at 90 days with intravenous tirofiban compared with placebo among patients with large vessel anterior circulation occlusion undergoing endovascular therapy according to current guidelines. We observed potential benefits of tirofiban in large artery atherosclerosis patients, and further randomized controlled trials are warranted to validate the present results.

Objective:This study aimed to evaluate the correlation between the stress hyperglycemia and clinical outcomes after large vessel occlusion stroke (LVO) at 90 days.Methods:The RESCUE BT trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial, consisting of 948 patients from 55 centers in China. In this subgroup study, 542 consecutive stroke patients with glucose or glycated hemoglobin values were included. Stress hyperglycemia was evaluated both as a tri-categorical variable (≤1.07 vs 1.08-1.29 vs ≥1.30) and a continuous variable. The primary outcome was favorable functional outcome (modified Rankin Scale [mRS] ≤ 2) at 90 days. The secondary outcome contained excellent functional outcome (modified Rankin Scale [mRS] ≤ 1) and safety outcomes such as 90-day mortality and intracranial hemorrhage.Results:542 patients were included. Compared to patients with the lowest tertiles of stress hyperglycemia, calculated as glucose/GA ratio, the highest tertiles of stress hyperglycemia was obviously associated with a higher rate of poor functional outcome at 90-day (modified Rankin Scale [mRS] score 3-6) after adjusted for potential covariates (adjusted hazard ratio, 0.44; 95% confidence interval, 0.28-0.69, P < 0.001). This result was also consistent in the excellent clinical outcome of 90-day mRS score 2-6 (adjusted hazard ratio, 0.48; 95% confidence interval, 0.29-0.79, P =0.004).Conclusion:In patients with acute ischemic stroke, lower stress hyperglycemia, as measured by glucose/GA ratio, was more likely to have favorable outcome at 90-day.Trial registrationChinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167, December 27, 2017.

Background:In acute ischemic stroke patients with large vessel occlusion, the role of intravenous tirofiban or alteplase as an adjunct to endovascular treatment (EVT) is still uncertain.Methods:This post hoc analysis used data from 467 patients included in two multicenter, randomized clinical trials that assessed intravenous adjunctive medications in stroke thrombectomy (DEVT and RESCUE BT). Patients were treated with EVT alone (EVT-alone group), intravenous tirofiban plus EVT (tirofiban+EVT group), and intravenous alteplase plus EVT (alteplase+EVT group). The primary outcome was functional independence (modified Rankin scale score 0-2) at 90 days. Safety outcomes included intracranial hemorrhage and mortality.Results:Of 467 patients included in the cohort, there were 172, 172, and 123 patients in EVT-alone, tirofiban+EVT, and alteplase+EVT group, respectively. Patients in the alteplase+EVT group were less likely to achieve functional independence than patients in the tirofiban+EVT group (adjusted risk ratio [RR], 0.80; 95% confidence interval [CI], 0.65-0.99; P= 0.04). Patients in the EVT-alone group compared with the tirofiban+EVT group (adjusted RR, 1.12; 95% CI, 0.92-1.36; P= 0.27) or the alteplase+EVT group (adjusted RR, 0.81; 95% CI, 0.65-1.02; P= 0.07) were similarly likely to obtain functional independence. Patients in the alteplase+EVT group had a higher risk of any intracranial hemorrhage than in the EVT-alone group (adjusted RR, 1.49; 95% CI, 1.03-2.14; P= 0.03) and tirofiban+EVT group (adjusted RR, 1.49; 95% CI, 1.02-2.18; P= 0.04). No significant difference was detected in the incidence of symptomatic intracranial hemorrhage and mortality among the three groups.Conclusions:Tirofiban before thrombectomy is associated with a better functional outcome and lower risk of any intracranial hemorrhage than alteplase among patients with large vessel occlusion treated within 4.5 hours after stroke onset.Trial Registration:chictr.org.cn, ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Background:Incomplete reperfusion contributes to reduced neurological recovery of patients with acute large vessel occlusion and successful reperfusion after endovascular thrombectomy. Intravenous tirofiban might enhance macrocirculatory and microcirculatory reperfusion in these patients, especially in those with large artery atherosclerotic stroke. We aimed to investigate whether treatment with adjunct intravenous tirofiban is associated improved outcomes following successful reperfusion in patients with acute large artery atherosclerotic stroke.Methods:In this subgroup analysis of RESCUE BT trial, patients with intracranial large artery atherosclerotic stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 were included. The primary outcome was the difference in proportion of independent functional outcome, defined as a modified Rankin score of 0 to 2 at 90 days. Safety outcomes included the rates of symptomatic intracranial hemorrhage and 90-day mortality.Results:Among the 382 patients with intracranial large artery atherosclerosis stroke and successful reperfusion (median [IQR] age, 65 (55-72) years; 105 [27.5%] women), 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95/175) with tirofiban and 44.0% (91/207) with placebo (adjusted odds ratio [aOR], 1.59; 95% CI, 1.03-2.45; P= 0.04). Intravenous tirofiban was not significantly associated with an increased risk of symptomatic intracranial hemorrhage within 48 hours (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; P= 0.44) or 90-day mortality (21/175 [12.0] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; P= 0.27).Conclusions:Among patients with acute large artery atherosclerotic stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of symptomatic intracranial hemorrhage or mortality. Confirmatory randomized trials in these patients are desirable.

Introduction:Efficacy and safety of tirofiban in endovascular therapy among cardio-embolized ischemic stroke patients remains controversial. We aimed to assess effects of tirofiban before endovascular therapy in cardio-embolized stroke patients.Methods:This is a post hoc analysis of Endovascular Treatment With vs Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial. Before endovascular therapy, participants were randomized to tirofiban or placebo group in ratio of 1:1. Tirofiban was administrated as a bolus dose of 10 ug/kg, followed by continuous infusion of 0.15 ug/kg /min for up to 24-hour. We collected cardio-embolized stroke patients according to Trial of Org 10172 in Acute Stroke Treatment classification. The efficacy outcome was global disability at 90-day assed by modified Rankin Scale (mRS). The primary safety outcome was symptomatic intracranial hemorrhage (sICH) assessed by Heidelberg bleeding classification within 48-hour. Secondary safety outcome was any radiologic intracranial hemorrhage and death at 90-day.Results:406 cardio-embolized stroke patients were collected. Tirofiban did not correlated to favorable shift to lower 90-day mRS (adjusted odds ratio [aOR], 0.91; 95% CI, 0.64-1.3; P= 0.617). However, tirofiban subgroup had a significantly higher risk of sICH within 48-hour (aOR, 3.26; 95% CI, 1.4-7.57; P= 0.006) compared with placebo group. The aOR was 1.44 (95% CI, 0.94-2.19; P= 0.094) for any intracranial hemorrhage and1.48 (95% CI, 0.88-2.52; P= 0.143) for death at 90-day.Conclusions:Tirofiban increased symptomatic intracranial hemorrhage after endovascular therapy in cardio-embolized stroke patients.Figure 1. Outcomes of endovascular therapy in cardio-embolic stroke participants in tirofiban vs placebo group.

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Background:Endovascular treatment (EVT) has become the standard treatment for large vessel occlusion (LVO) in acute ischemic stroke. However, results on long-term clinical outcomes are lacking.Objective:We sought to assess the 5-year functional outcome of patients with acute LVO in anterior circulation undergoing EVT.MetholdThis study was an observational, nationwide registry of consecutive patients aged 18 years or older who received EVT for acute LVO in anterior circulation in 27 comprehensive stroke centers across 12 provinces in China. The primary outcome was the proportion of good functional outcome defined as modified Rankin Scale scores (mRS) of 2 or less at 5 years. Secondary outcomes included the proportion of patients with excellent clinical outcome (mRs0-1), all-cause mortality and risk of stroke recurrence at 5 years.Results:A total of 807 patients were recruited into the study. Of these, 642 patients (79.6%) had 5-year follow-up data. Both the proportions of good outcome (40.7% VS 43.2%, P=0.321).and excellent outcome (29.6% VS 27.0%, P=0.278) at 5 years were similar to the proportions at 90 days after stroke; The cumulative 5-year mortality (47.0% VS 24.7%, P<0.001) and stroke recurrence rate (19.9% VS 1.6%, P<0.001) were significantly higher than rates at 90 days, and 66.4% of the stroke recurrent patients died at 5 years. Multivariate analyses identified increasing age, residual disability at 90 days and stroke recurrence were predictors for good functional outcome and the increased mortality risk at 5 years.

Background and Purpose:This study aimed to investigate the efficacy and safety of endovascular treatment (EVT) in patients with acute basilar artery occlusion and moderate deficit (National Institutes of Health Stroke Scale [NIHSS] score 10 to 20) versus standard medication treatment (SMT) alone.Methods:Patients from a nationwide prospective registry termed BASILAR (the Endovascular Treatment for Acute Basilar Artery Occlusion Study) were divided into three kinds of population according to NIHSS, including patients with mild deficit (NIHSS score <10), moderate deficit (NIHSS score 10-20) and severe deficit (NIHSS score>20). Then patients with moderate deficit were identified and divided into two groups for analysis: EVT group or SMT-alone group. The primary efficacy outcome was a favorable functional outcome (modified Rankin Scale score 0-3) at 90 days and safety outcomes were symptomatic intracerebral hemorrhage and mortality at 90 days.Results:A total of 194 patients had moderate deficit of which 47 patients treated with SMT-alone and 147 patients treated with EVT. Compared with patients in the SMT-alone group, patients undergoing EVT were associated with significant higher proportion of 90-day modified Rankin Scale scores of 3 or less (adjusted odds ratio, 3.36 [95%CI, 1.14-9.92]; P= .028) but no statistically significant difference was found in 90-day mortality (adjusted odds ratio, 0.53 [95% CI, 0.25-1.14]; P= .10) despite a higher rate of symptomatic intracerebral hemorrhage (4 of 146 patients [2.7%] vs 0 of 47 patients [0%]).Conclusions:This study suggests that EVT in acute basilar artery occlusion patients with moderate deficit may be associated with better functional outcomes. More randomized clinical trials were in need to explore the management of these patients.

Background:As a glycoprotein IIb/IIIa receptor inhibitor, tirofiban may help reduce the risk of vascular complications during percutaneous transluminal coronary intervention. However, evidence on whether tirofiban improve the outcomes of stroke patients with large vessel occlusion who are receiving endovascular treatment is limited.Objective:This trial aims to assess whether additional intravenous tirofiban therapy can improve the clinical outcomes of stroke patients with large vessel occlusion who undergo endovascular treatment within 24 hours of symptom onset.Methods and Design:The Endovascular Treatment With versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) Trial is an investigator-initiated, randomized, placebo-controlled, double-blind, multicenter trial. Up to 930 eligible patients will be consecutively randomized to tirofiban or control group in 1:1 ratio over three years from approximate 50 endovascular-capable stroke centers in China.Outcomes:The primary end-point is the disability level measured by overall distribution of the 90-day modified Rankin Scale score. The primary safety end-points are symptomatic intracerebral hemorrhage at 48 hours and mortality at 90 days.Trial status:The trial screening and enrollment began on 10 October, 2018, and now the randomization is still ongoing. We expect that the enrollment will be end in October 2021, and the trial results will be revealed in February 2022.Trial registry number:ChiCTR-INR-17014167 (www.chictr.org.cn).

Nitrogen-rich azoles, i.e., triazole (Ta) and tetrazole (Tta), as electrolyte additives afford the strong chemisorption to lithium polysulfides, thus guiding the configurations of Li2Sx-Ta/Tta complexes. In electrolyte, the azoles also enhance the ionic conductivity and lithium transference number. In addition, the Ta/Tta also participate the formation of SEI and promote the uniform Li deposition. The introduction of azoles endows the improved cycling performance of Li-S and Li-organosulfide batteries.

We report the identification of the tndbiosynthetic cluster from the marine-derived fungus Aspergillus flavipesand the in vivo characterization of a cryptic type I diterpene synthase. The heterologous expression of the bifunctional terpene synthase led to the discovery of a diterpene backbone, talarodiene, harboring a benzo[a]cyclopenta[d]cyclooctane tricyclic fused ring system. The conversion of geranylgeranyl diphosphate to talarodiene was investigated using 13C-labeling studies, and stable isotope tracer experiments showed the biotransformation of talarodiene into talaronoid C.