Endovascular treatment versus standard medical treatment in patients with established large infarct: a cohort study.

BACKGROUND: Previous trials confirmed the benefit of endovascular treatment (EVT) in acute large core stroke, but the effect of EVT on outcomes in these patients based on non-contrast computed tomography (NCCT) in real-world clinical practice was unclear. The aim of this study was to explore the effect of EVT versus standard medical treatment (SMT) in patients with large ischemic core stroke defined as Alberta Stroke Program Early CT Score (ASPECTS)≤5 based on NCCT alone. MATERIALS AND METHODS: Patients with acute large core stroke at 38 Chinese centers between November 2021 and February 2023 were reviewed from prospectively maintained databases. The primary outcome was favorable functional outcome (modified Rankin Scale score [mRS], 0-3) at 90 days. Safety outcomes included 48-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. RESULTS: Of 745 eligible patients recruited at 38 stroke centers between November 2021 and February 2023, 490 were treated with EVT and 255 with SMT alone. One hundred and eighty-one (36.9%) in the EVT group achieved favorable functional independence versus 48 (18.8%) treated with SMT only (adjusted risk ratio [RR], 1.86; 95% CI, 1.43 to 2.42, P<0.001; adjusted risk difference [RD], 13.77; 95% CI, 7.40 to 20.15, P<0.001). The proportion of sICH was significantly higher in patients undergoing EVT (13.3% vs. 2.4%; adjusted RR, 5.17; 95% CI, 2.17 to 12.32, P<0.001; adjusted RD, 10.10; 95% CI, 6.12 to 14.09, P<0.001). No significant difference of mortality between the groups was observed (41.8% vs. 49.0%; adjusted RR, 0.91; 95% CI, 0.77 to 1.07, P=0.24; adjusted RD, -5.91; 95% CI, -12.91 to 1.09, P=0.1). CONCLUSION: Among patients with acute large core stroke based on NCCT in real world, EVT is associated with better functional outcomes at 90 days despite of higher risk of sICH. Rates of procedure-related complications were high in the EVT group.

Association of functional outcomes between intravenous tirofiban and endovascular thrombectomy in imaging-screened patients with large vessel occlusion stroke: a secondary analysis of randomized clinical trial.

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 perioperative intravenous tirofiban would further enhance the clinical benefit of endovascular therapy in the RESCUE BT trial according to advanced imaging criteria based on current American Heart Association/American Stroke Association (AHA/ASA) guidelines. METHODS: This is a secondary analysis of the RESCUE BT trial. Patients who were eligible for endovascular thrombectomy in the 6-hour window and met the criteria of the DAWN or DEFUSE 3 trials in the extended window according to the AHA/ASA guidelines were analyzed. The primary outcome was the distribution of the 90-day modified Rankin Scale (mRS) scores. Safety outcomes included the incidence 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 meeting the AHA/ASA 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 the tirofiban group, and 3 (IQR, 1-4) in the placebo group. The adjusted common odds ratio (OR) for a lower level of disability with tirofiban than with placebo was 1.08 (95% confidence interval [CI], 0.83-1.42). The incidence of sICH (10.1% versus 6.3%; adjusted OR 1.70; [95% CI, 0.95-3.04]) was not significantly 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 patients with large artery atherosclerosis. CONCLUSIONS: There was no significant difference in the severity of disability at 90 days with intravenous tirofiban compared to placebo in patients who underwent endovascular therapy according to AHA/ASA guidelines. We observed potential benefits of tirofiban in patients with large artery atherosclerosis, but there was an increased risk of sICH in patients with cardioembolism stroke.

Clinical laboratory characteristics and gene mutation spectrum of Ph-negative MPN patients with atypical variants of JAK2, MPL, or CALR.

OBJECTIVE: To evaluate the incidence, clinical laboratory characteristics, and gene mutation spectrum of Ph-negative MPN patients with atypical variants of JAK2, MPL, or CALR. METHODS: We collected a total of 359 Ph-negative MPN patients with classical mutations in driver genes JAK2, MPL, or CALR, and divided them into two groups based on whether they had additional atypical variants of driver genes JAK2, MPL, or CALR: 304 patients without atypical variants of driver genes and 55 patients with atypical variants of driver genes. We analyzed the relevant characteristics of these patients. RESULTS: This study included 359 patients with Ph-negative MPNs with JAK2, MPL, or CALR classical mutations and found that 55 (15%) patients had atypical variants of JAK2, MPL, or CALR. Among them, 28 cases (51%) were male, and 27 (49%) were female, with a median age of 64 years (range, 21-83). The age of ET patients with atypical variants was higher than that of ET patients without atypical variants [70 (28-80) vs. 61 (19-82), p = 0.03]. The incidence of classical MPL mutations in ET patients with atypical variants was higher than in ET patients without atypical variants [13.3% (2/15) vs. 0% (0/95), p = 0.02]. The number of gene mutations in patients with atypical variants of driver genes PV, ET, and Overt-PMF is more than in patients without atypical variants of PV, ET, and Overt-PMF [PV: 3 (2-6) vs. 2 (1-7), p < 0.001; ET: 4 (2-8) vs. 2 (1-7), p < 0.05; Overt-PMF: 5 (2-9) vs. 3 (1-8), p < 0.001]. The incidence of SH2B3 and ASXL1 mutations were higher in MPN patients with atypical variants than in those without atypical variants (SH2B3: 16% vs. 6%, p < 0.01; ASXL1: 24% vs. 13%, p < 0.05). CONCLUSION: These data indicate that classical mutations of JAK2, MPL, and CALR may not be completely mutually exclusive with atypical variants of JAK2, MPL, and CALR. In this study, 30 different atypical variants of JAK2, MPL, and CALR were identified, JAK2 G127D being the most common (42%, 23/55). Interestingly, JAK2 G127D only co-occurred with JAK2V617F mutation. The incidence of atypical variants of JAK2 in Ph-negative MPNs was much higher than that of the atypical variants of MPL and CALR. The significance of these atypical variants will be further studied in the future.

Association between carotenoid intake and periodontitis in diabetic patients.

This study aimed to evaluate the association between dietary carotenoid intake and periodontitis in diabetic patients. Data on diabetic patients were collected from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 for this cross-sectional study. Dietary intake of carotenoids was assessed through the first 24-hour dietary recall interview. Full-mouth periodontal examinations were conducted by trained dental examiners. Subgroup analysis was conducted in terms of age, gender, the number of missing teeth, cardiovascular disease, smoking, and anti-diabetic drugs. Totally 1914 diabetic patients were included, with 1281 (66.93%) in the periodontitis group. After adjusting for age, gender, race, education, smoking, dental implants, hepatitis, and the number of missing teeth, α-carotene intake ≥55.82 mcg was associated with lower odds of periodontitis than α-carotene intake <55.82 mcg [OR = 0.70, 95% CI: 0.53-0.91, P = 0.010]; lutein and zeaxanthin intake ≥795.95 mcg was associated with decreased odds of periodontitis than lutein and zeaxanthin intake <795.95 mcg (OR = 0.75, 95%CI: 0.57-0.98, P = 0.039). The association between carotenoid intake and periodontitis varied across different subpopulations. In diabetes, dietary intake of α-carotene and lutein and zeaxanthin was inversely associated with the odds of periodontitis, which may facilitate clinical periodontitis management.

Systemic THrombolysis Randomization IN Endovascular Stroke Therapy (SHRINE) Collaboration: a patient-level pooled analysis of the SKIP and DEVT Trials.

OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: The 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.

Fluorescence switch based on NIR-emitting carbon dots revealing high selectivity in the rapid response and bioimaging of oxytetracycline.

The abuse of antibiotics has led to serious environmental pollution and the emergence of drug-resistant bacteria surpassing the replacement rate of antibiotics. Herein, near-infrared fluorescent carbon dots (NIR-CDs) were developed to meet the requirements for oxytetracycline (OTC) detection in food and water samples (milk, honey, and lake water) with a detection limit of 0.112 µM. These NIR-CDs, possessing excellent water-solubility, deep tissue penetration ability, and tunable optical properties, exhibit maximum emission at 790 nm (NIR-I window). Unlike traditional CDs, this novel NIR-CDs nanoprobe provides a dual response in the presence of OTC (quenching and bathochromic shifting), without obvious interference from other existing biomolecules and metal ions. Additionally, these NIR-CDs exhibit excellent photostability and multi-resistance under UV irradiation, exceptional pH stability (pH 6-12), reliable long-time exposure, and durability in ionic (NaCl) environments. Moreover, NIR-CDs and NIR-CDs@OTC are nontoxic and were successfully utilized for cell-imaging applications in normal (NIH3T3) and cancer cells (HeLa).

Thrombectomy alone versus intravenous thrombolysis before thrombectomy for acute basilar artery occlusion.

BACKGROUND: Endovascular 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). METHODS: This 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. RESULTS: Direct 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). CONCLUSIONS: Among 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.

A fluorescence biosensor based on DNA aptamers-COF for highly selective detection of ATP and thrombin.

Due to their distinctive physical, chemical, electrical, and optical properties as well as their prospective uses, 2D covalent organic framework (COF) have attracted much attention. Herein, TaTPA-COF was effectively synthesized from the condensation of TTA and TFPA using a facile solvothermal method and characterized by SEM image, FT-IR spectra, and PXRD pattern. The generated bulk TaTPA-COF materials combined with DNA aptamers are utilized as the acceptor (quencher) for the highly sensitive and selective detection of adenosine 5'-triphosphate (ATP) and thrombin, with a novel fluorescence biosensing platform and a proof-of-concept application.

Development and validation of machine learning-based model for mortality prediction in patients with acute basilar artery occlusion receiving endovascular treatment: multicentric cohort analysis.

BACKGROUND: Predicting 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. METHODS: The 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. RESULTS: Extreme 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. CONCLUSION: We 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.

Locked-in syndrome responding to endovascular treatment.

BACKGROUND: Locked-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. OBJECTIVE: To assess the outcomes associated with EVT and identify the factors associated with outcomes of LiS. METHODS: We 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. RESULTS: Among 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. CONCLUSIONS: This 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.

Root-secreted (-)-loliolide modulates both belowground defense and aboveground flowering in Arabidopsis and tobacco.

Plant defense, growth, and reproduction can be modulated by chemicals emitted from neighboring plants, mainly via volatile aboveground signals. However, belowground signals and their underlying control mechanisms are largely unknown. Here, we experimentally demonstrate that the root-secreted carotenoid (-)-loliolide mediates both defensive and reproductive responses in wild-type Arabidopsis, a carotenoid-deficient Arabidopsis mutant (szl1-1), and tobacco (Nicotiana benthamiana). Wild-type Arabidopsis plants flower later than szl1-1, and they secrete (-)-loliolide into the soil, whereas szl1-1 roots do not. When Arabidopsis and tobacco occur together, wild-type Arabidopsis induces nicotine production and defense-related gene expression in tobacco, whereas szl1-1 impairs this induction but accelerates tobacco flowering. Furthermore, nicotine production and the expression of the key genes involved in nicotine biosynthesis (QPT, PMT1), plant defense (CAT1, SOD1, PR-2a, PI-II, TPI), and flowering (AP1, LFY, SOC1, FT3, FLC) are differently regulated by incubation with wild-type Arabidopsis and szl1-1 root exudates or (-)-loliolide. In particular, (-)-loliolide up-regulated flowering suppressors (FT3 and FLC) and transiently down-regulated flowering stimulators (AP1 and SOC1), delaying tobacco flowering. Therefore, root-secreted (-)-loliolide modulates plant belowground defense and aboveground flowering, yielding critical insights into plant-plant signaling interactions.

Effect of the anastomosis between the posterior inferior cerebellar artery and the superior cerebellar artery on outcomes of acute basilar artery occlusion after endovascular treatment.

BACKGROUND: The 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. METHODS: This 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. RESULTS: Of 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). CONCLUSIONS: The PICA-SCA anastomosis is significantly associated with better functional outcomes in patients with acute BAO after EVT, especially in those with middle BAO.

Correlation Analysis and Prognostic Impacts of Biological Characteristics in Elderly Patients with Acute Myeloid Leukemia.

Background: The significant heterogeneity of elderly AML patients' biological features has caused stratification difficulties and adverse prognosis. This paper did a correlation study between their genetic mutations, clinical features, and prognosis to further stratify them. Methods: 90 newly diagnosed elderly acute myeloid leukemia (AML) patients (aged ≥60 years) who detected genetic mutations by next-generation sequencing (NGS) were enrolled between April 2015 and March 2021 in our medical center. Results: A total of 29 genetic mutations were identified in 82 patients among 90 cases with a frequency of 91.1%. DNMT3A, BCOR, U2AF1, and BCORL1 mutations were unevenly distributed among different FAB classifications (p < 0.05). DNMT3A, IDH2, NPM1, FLT3-ITD, ASXL1, IDH1, SRSF2, BCOR, NRAS, RUNX1, U2AF1, MPO, and WT1 mutations were distributed differently when an immunophenotype was expressed or not expressed (p<0.05). NPM1 and FLT3-ITD had higher mutation frequencies in patients with normal chromosome karyotypes than abnormal chromosome karyotypes (p<0.001, p=0.005). DNMT3A and NRAS mutations predicted lower CR rates. DNMT3A, TP53, and U2AF1 mutations were related to unfavorable OS. TET2 mutation with CD123+, CD11b+ or CD34- predicted lower CR rate. IDH2+/CD34- predicted lower CR rate. ASXL1+/CD38+ and SRSF2+/CD123- predicted shorter OS. Conclusion: The study showed specific correlations between elderly AML patients' genetic mutations and clinical features, some of which may impact prognosis.

Structurally diverse metabolites from a soil-derived fungus Aspergillus calidoustus.

Fifteen secondary metabolites, including five new sesquiterpenoids (1-5), one new benzofuranoid (10), one new ophiobolin sesterterpenoid (11), and one new 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoid (15), as well as seven known analogues (6-9 and 12-14), were isolated and characterized from fungus Aspergillus calidoustus, which was separated from the wetland soil collected at Dianchi Lake, Yunnan Province. Compound 5 featured an unusual dioxolane moiety, and compound 15 was a rare austin meroterpenoid analogue with the opened A ring, and also featured an undescribed oxygen bridge between C-3 and C-16 to construct an unexpected tetrahydrofuran ring. Their structures were established by widespread spectroscopic methods, single-crystal X-ray diffraction experiments, and ECD calculation. All the isolated drimane sesquiterpenoids were evaluated for the in vitro cytotoxicity against five tumor cell lines, including SW480 (colon cancer), IOMM-Lee (meningioma), HeLa (cervical cancer), FARAGE (diffuse large B-cell lymphoma), and SU-DHL-4 (diffuse large B-cell lymphoma). Compound 9 exhibited significant cytotoxicity against FARAGE and SU-DHL-4 tumor cell lines with IC50 values of 5.54 and 9.78 µM, respectively. Further mechanism study showed that 9 could significantly promote apoptosis in FARAGE and SU-DHL-4 cell lines by interfering with mitochondrial function.

Neutrophil Count Predicts Malignant Cerebellar Edema and Poor Outcome in Acute Basilar Artery Occlusion Receiving Endovascular Treatment: A Nationwide Registry-Based Study.

Background: Acute basilar artery occlusion (ABAO) is known to have a poor outcome with a high rate of morbidity and mortality despite endovascular treatment (EVT), highlighting the necessities of exploring factors to limit the efficacy of EVT in these patients. Cerebellar infarctions in ABAO might progress to malignant cerebellar edema (MCE), a life-threatening complication after reperfusion, posing a secondary injury to the brainstem by mass effects. Therefore, the present research aimed to explore the impacts of MCE on a long-term outcome and investigate the prognostic factors for MCE among ABAO after EVT. Methods: In the national BASILAR registry, a total of 329 ABO patients with cerebellar infarctions treated by EVT met the inclusion criteria. The presence of MCE defined by the Jauss scale ≥4 points, was evaluated on the computed tomography performed 72 h after EVT. The adjusted odds ratio and 95% CI were obtained by logistic regression models. A favorable outcome was defined as a 90-day modified Rankin Scale score of 0-3. Results: MCE was statistically associated with the decreased incidence of a favorable outcome [adjusted odds ratio, 0.35(95% CI, 0.18-0.68), P=0.002]. The baseline National Institutes of Health Stroke Scale score, collateral circulation, neutrophil count at admission, and recanalization status were predictors for MCE and a favorable functional status at 90 days (all P<0.05). Among all inflammatory factors, the neutrophil count achieved the highest accuracy, sensitivity, and specificity for MCE. Adding the neutrophil count status into the baseline model obviously enhanced its prediction ability for MCE and favorable outcome by increasing the area under curve and achieving both net reclassification and integrated discrimination improvement (all P<0.05). Mediation analysis indicated that MCE mediated the association between the increased neutrophil count and worse functional outcome (P=0.026). Discussion: MCE acted essential roles in worsening prognosis for ABAO after EVT. A high neutrophil count at admission was linked to MCE and a poor outcome among ABAO patients, which could be further incorporated into the clinical decision-making system and guide immunomodulation therapy.

Decreased EMILIN2 correlates to metabolism phenotype and poor prognosis of ovarian cancer.

This study aimed to explore the function and related mechanisms of elastin microfibril interfacer 2 (EMILIN2) in ovarian cancer. First, the expression level of EMILIN2 was detected in patient tissues and its correlation with overall survival rate was analysed. Then, EMILIN2 was overexpressed in ovarian cancer cell lines to observe its function and effect on Warburg effect. By detecting its promoter region methylation, the epigenetic regulatory role was explored. Finally, through the luciferase reporter assay and siRNA tools, the regulatory mechanism of p53 on EMILIN2 was investigated. It was detected in clinical samples that down-regulated EMILIN2 was associated with poor prognosis of ovarian cancer. It was further found that EMILIN2 regulated the metabolic phenotype of ovarian cancer cells. The expression of EMILIN2 was epigenetically regulated by its promoter methylation. Also, it was found that p53 regulated the expression of EMILIN2 and the p53/EMILIN2 axis regulated the Warburg effect in ovarian cancer cells. EMILIN2 was inhibited by methylation in ovarian cancer. In summary, p53 can promote and regulate its transcription by binding to the promoter region of EMILIN2, thereby affecting the Warburg effect and inhibiting tumours. Therefore, EMILIN2 might be a potential target for clinical diagnosis and treatment of ovarian cancer.

Extended Thrombolysis In Cerebral Infarction (eTICI) grade 2c: a potential angiographic target for endovascular treatment in acute basilar artery occlusion?

BACKGROUND: Higher 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. METHODS: We 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. RESULTS: Among 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. CONCLUSIONS: An 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.

Impact of anesthetic strategy on outcomes for patients with acute basilar artery occlusion undergoing mechanical thrombectomy.

BACKGROUND: The 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. METHODS: Patients 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. RESULTS: 639 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. CONCLUSIONS: The 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.

Asperanstinoids A-E: Undescribed 3,5-dimethylorsellinic acid-based meroterpenoids from Aspergillus calidoustus.

Large-scale culture is a complementary and practical method for genome mining and OSMAC approaches to discover novel natural products through accumulation and reprocessing effects. By employing a large-scale culture approach, twelve 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoids, including five undescribed compounds, namely asperanstinoids A-E, were obtained from fungus Aspergillus calidoustus, which was isolated from the wetland soil collected at Dianchi Lake, Yunnan Province. The structures and absolute configurations of asperanstinoids A-E were determined by various spectroscopic analyses, including NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations, and the absolute configurations of three known compounds, dehydroaustinol, austinol, and austin, were confirmed via single-crystal X-ray diffraction for the first time. Notably, asperanstinoid A represents the second example of a DMOA-based meroterpenoid featuring a unique 6/5/6/6/6/5-fused hexacyclic skeleton with a rare "1,13-epoxy" moiety. The cytotoxicity assay of all these isolates revealed that asperanstinoid D, dehydroaustinol, and austin displayed considerable cytotoxicity against the HL-60 and SU-DHL-4 tumor cell lines with IC50 values ranging from 15.7 to 27.8 µM.

Anti-diabetic Role of Adropin in Streptozotocin Induced Diabetic Rats via Alteration of PI3K/Akt and Insulin Signaling Pathway.

Diabetes mellitus (DM) is a hyperglycemia-related multifactorial condition with an elevated risk of microvascular and microvascular complications associated with this disease. The current experimental study was to examine the antidiabetic activity of streptozotocin (STZ)-induced adropin against diabetic rats by altering the PI3K/Akt and insulin signaling pathways. STZ (60 mg/kg) was used for the induction of DM and rats were divided into different groups and received the adropin (20, 40 and 80 mg/kg) and glibenclamide (10 mg/kg) till 28 days. Body weight, plasma insulin, blood glucose and food intake were estimated, respectively. Biochemical enzymes, carbohydrate enzymes, lipid parameters, AMPK and insulin signalling pathway parameters were estimated. GLUT4 and PPARγ expression were also estimated. Oral administration of adropin significantly (p < 0.001) increased the glycogen, glucose-6-phosphatase dehydrogenase, insulin, hexokinase and belittled the blood glucose level, fructose 1-6-biphosphatase, glucose-6-phosphatase at dose dependent manner. Adropin significantly (p < 0.001) reduced the level of triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein and increased the level of high density lipoprotein at dose dependent manner. Adropin significantly (p < 0.001) activated the Akt, IRS-2, IRS-1, IR, p-AKT and PI3k, which are the key modulator molecules of PI3K/Akt, AMPK and insulin signalling pathway in DM rats. The current experimental study confirms the anti-diabetic effect of adropin on DM rats induced by AMPK and insulin signalling pathway against STZ.