Technical Risk Stratification Nomogram Model for 90-Day Mortality Prediction in Patients With Acute Basilar Artery Occlusion Undergoing Endovascular Thrombectomy: A Multicenter Cohort Study.

BACKGROUND: This study aimed to establish and validate a nomogram model for predicting 90-day mortality in patients with acute basilar artery occlusion receiving endovascular thrombectomy. METHODS AND RESULTS: A total of 242 patients with basilar artery occlusion undergoing endovascular thrombectomy were enrolled in our study, in which 172 patients from 3 stroke centers were assigned to the training cohort, and 70 patients from another center were assigned to the validation cohort. Univariate and multivariate logistic regression analyses were adopted to screen prognostic predictors, and those with significance were subjected to establish a nomogram model in the training cohort. The discriminative accuracy, calibration, and clinical usefulness of the nomogram model was verified in the internal and external cohorts. Six variables, including age, baseline National Institutes of Health Stroke Scale score, Posterior Circulation-Alberta Stroke Program Early CT (Computed Tomography) score, Basilar Artery on Computed Tomography Angiography score, recanalization failure, and symptomatic intracranial hemorrhage, were identified as independent predictors of 90-day mortality of patients with basilar artery occlusion and were subjected to develop a nomogram model. The nomogram model exhibited good discrimination, calibration, and clinical usefulness in both the internal and the external cohorts. Additionally, patients were divided into low-, moderate-, and high-risk groups based on the risk-stratified nomogram model. CONCLUSIONS: Our study proposed a novel nomogram model that could effectively predict 90-day mortality of patients with basilar artery occlusion after endovascular thrombectomy and stratify patients with high, moderate, or low risk, which has a potential to facilitate prognostic judgment and clinical management of stroke.

Linc00673-V3 positively regulates autophagy by promoting Smad3-mediated LC3B transcription in NSCLC.

Since its first discovery, long noncoding RNA Linc00673 has been linked to carcinogenesis and metastasis of various human cancers. Linc00673 had five transcriptional isoforms and their biological functions remained to be explored. Here we have reported that Linc00673-V3, one of the isoforms of Linc00673, promoted non-small cell lung cancer chemoresistance, and increased Linc00673-V3 expression level was associated with enhanced autophagy. Mechanistically, we discerned the existence of a stem-loop configuration engendered by the 1-100-nt and 2200-2275-nt fragments within Linc00673-V3. This structure inherently interacted with Smad3, thereby impeding its ubiquitination and subsequent degradation orchestrated by E3 ligase STUB1. The accumulation of Smad3 contributed to autophagy via up-regulation of LC3B transcription and ultimately conferred chemoresistance in NSCLC. Our results revealed a novel transcriptional regulation network between Linc00673-V3, Smad3, and LC3B, which provided an important insight into the interplay between autophagy regulation and non-canonical function of Smad3. Furthermore, the results from in vivo experiments suggested Linc00673-V3 targeted antisense oligonucleotide as a promising therapeutic strategy to overcome chemotherapy resistance in NSCLC.

Periprocedural thromboembolic complications of LEO baby stent in endovascular treatment of intracranial aneurysms: Experience in 149 patients.

OBJECTIVE: To report periprocedural thromboembolic complications of LEO Baby stent-assisted coiling of wide-necked intracranial aneurysms and to analyze the possible influencing factors. METHODS: We retrospectively identified 149 patients with aneurysms who underwent LEO Baby stent-assisted embolization between October 2018 and March 2022. Clinical and radiographic data of patients were reviewed to determine whether a thromboembolic event had occurred. Multivariate logistic analysis was performed to identify significant factors associated with thromboembolic events. RESULTS: Successful stent deployment of the stent was achieved in all patients in the target artery. There were 66 patients (44.3%) with acutely ruptured aneurysms and 83 patients (55.7%) with unruptured aneurysms. Fourteen (9.4%, 95% confidence interval: 4.7%-14.1%) patients were confirmed to have developed a thromboembolic event, including nine patients with acute intraoperative thrombosis and five patients with postoperative thromboembolic events. The rate of thromboembolic events was 6.0% (5/83) in patients with unruptured aneurysms and 13.6% (9/66) in patients with acutely ruptured aneurysms. There was a trend toward an increased rate of thromboembolic events in patients with acute ruptured aneurysms (p = 0.087). Thromboembolic events were significantly associated with the parent-artery diameter (p = 0.010). CONCLUSIONS: Our study demonstrates a low rate of thromboembolic complications in unruptured aneurysms treated with LEO Baby stent. Thromboembolic events appear to be more common in ruptured aneurysms. A small diameter of the parent artery is associated with an increased risk of thromboembolic complications, and more relevant studies are still needed.

Aneurysmal subarachnoid hemorrhage complicating spinal subarachnoid hematoma causing acute cauda equina syndrome: a case report.

BACKGROUND: Spinal subarachnoid hematoma (SSH) is a known but rare entity that can cause cauda equina compression. The occurrence of SSH associated with aneurysmal subarachnoid hemorrhage has rarely been described in the literature. CASE PRESENTATION: A 56-year-old woman presented with subarachnoid hemorrhage secondary to a ruptured middle cerebral artery aneurysm and was managed with coiling embolization without stent assistance. There was no history of either lumbar puncture or the use of anticoagulants. The patient developed severe lumbago radiating to bilateral legs nine days after the procedure. Subsequent magnetic resonance imaging demonstrated a SSH extending from L5 to S2 and wrapping around the cauda equina. The patient was treated with intravenous methylprednisolone (250 mg/day) for four consecutive days, followed by a taper of oral prednisolone (20 mg/day) until complete recovery. Magnetic resonance imaging at one month follow-up revealed complete resolution of the SSH. CONCLUSIONS: Here, we report a case of acute cauda equina syndrome caused by a SSH after aneurysmal subarachnoid hemorrhage, which will facilitate timely intervention of patients with this disorder.

Microalgae Inoculation Significantly Shapes the Structure, Alters the Assembly Process, and Enhances the Stability of Bacterial Communities in Shrimp-Rearing Water.

Intensive shrimp farming may lead to adverse environmental consequences due to discharged water effluent. Inoculation of microalgae can moderate the adverse effect of shrimp-farming water. However, how bacterial communities with different lifestyles (free-living (FL) and particle-attached (PA)) respond to microalgal inoculation is unclear. In the present study, we investigated the effects of two microalgae (Nannochloropsis oculata and Thalassiosira weissflogii) alone or in combination in regulating microbial communities in shrimp-farmed water and their potential applications. PERMANOVA revealed significant differences among treatments in terms of time and lifestyle. Community diversity analysis showed that PA bacteria responded more sensitively to different microalgal treatments than FL bacteria. Redundancy analysis (RDA) indicated that the bacterial community was majorly influenced by environmental factors, compared to microalgal direct influence. Moreover, the neutral model analysis and the average variation degree (AVD) index indicated that the addition of microalgae affected the bacterial community structure and stability during the stochastic process, and the PA bacterial community was the most stable with the addition of T. weissflogii. Therefore, the present study revealed the effects of microalgae and nutrient salts on bacterial communities in shrimp aquaculture water by adding microalgae to control the process of community change. This study is important for understanding the microbial community assembly and interpreting complex interactions among zoo-, phyto-, and bacterioplankton in shrimp aquaculture ecosystems. Additionally, these findings may contribute to the sustainable development of shrimp aquaculture and ecosystem conservation.

Toward three-dimensional DNA industrial nanorobots.

Nanoscale industrial robots have potential as manufacturing platforms and are capable of automatically performing repetitive tasks to handle and produce nanomaterials with consistent precision and accuracy. We demonstrate a DNA industrial nanorobot that fabricates a three-dimensional (3D), optically active chiral structure from optically inactive parts. By making use of externally controlled temperature and ultraviolet (UV) light, our programmable robot, ~100 nanometers in size, grabs different parts, positions and aligns them so that they can be welded, releases the construct, and returns to its original configuration ready for its next operation. Our robot can also self-replicate its 3D structure and functions, surpassing single-step templating (restricted to two dimensions) by using folding to access the third dimension and more degrees of freedom. Our introduction of multiple-axis precise folding and positioning as a tool/technology for nanomanufacturing will open the door to more complex and useful nano- and microdevices.

Radiomics features on computed tomography reflect thrombus histological age prior to endovascular treatment of acute ischemic stroke.

PURPOSE: To investigate the role of radiomics features in thrombus age identification and establish a CT-based radiomics model for predicting thrombus age of large vessel occlusion stroke patients. METHODS: We retrospectively reviewed patients with middle cerebral artery occlusion receiving mechanical thrombectomy from July 2020 to March 2022 at our center. The retrieved clots were stained with Hematoxylin and Eosin (H&E) and determined as fresh or older thrombi based on coagulation age. Clot-derived radiomics features were selected by least absolute shrinkage and selection operator (LASSO) regression analysis, by which selected radiomics features were integrated into the Rad-score via the corresponding coefficients. The prediction performance of Rad-score in thrombus age was evaluated with the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 104 patients were included in our analysis, with 52 in training and 52 in validation cohort. Older thrombi were characterized with delayed procedure time, worse functional outcome and marginally associated with more attempts of device. We extracted 982 features from NCCT images. Following T test and LASSO analysis in training cohort, six radiomics features were selected, based on which the Rad-score was generated by the linear combination of features. The Rad-score showed satisfactory performance in distinguishing fresh with older thrombi, with the AUC of 0.873 (95 %CI: 0.777-0.956) and 0.773 (95 %CI: 0.636-0.910) in training and validation cohort, respectively. CONCLUSION: This study established and validated a CT-based radiomics model that could accurately differentiate fresh with older thrombi for stroke patients receiving mechanical thrombectomy.

Low dose PFDA induces DNA damage and DNA repair inhibition by promoting nuclear cGAS accumulation in ovarian epithelial cells.

Per- and polyfluoroalkyl substances (PFAS), the versatile anthropogenic chemicals, are popular with the markets and manufactured in large quantities yearly. Accumulation of PFAS has various adverse health effects on human. Albeit certain members of PFAS were found to have genotoxicity in previous studies, the mechanisms underlying their effects on DNA damage repair remain unclear. Here, we investigated the effects of Perfluorodecanoic acid (PFDA) on DNA damage and DNA damage repair in ovarian epithelial cells through a series of in vivo and in vitro experiments. At environmentally relevant concentration, we firstly found that PFDA can cause DNA damage in primary mouse ovarian epithelial cells and IOSE-80 cells. Moreover, nuclear cGAS increased in PFDA-treated cells, which leaded to the efficiency of DNA homologous recombination (HR) decreased and DNA double-strand breaks perpetuated. In vivo experiments also verified that PFDA can induce more DNA double-strand breaks lesions and nuclear cGAS in ovarian tissue. Taken together, our results unveiled that low dose PFDA can cause deleterious effects on DNA and DNA damage repair (DDR) in ovarian epithelial cells and induce genomic instability.

Subcortical infarcts on admission CTP predict poor outcome despite excellent reperfusion in delayed time windows.

PURPOSE: The effect of pretreatment infarct location on clinical outcome after successful mechanical thrombectomy is not understood. Our aim was to evaluate the association between computed tomography perfusion (CTP)-based ischemic core location and clinical outcome following excellent reperfusion in late time windows. METHODS: We retrospectively reviewed patients who underwent thrombectomy for acute anterior circulation large vessel occlusion in late time windows from October 2019 to June 2021 and enrolled 65 patients with visible ischemic core on admission CTP who had received excellent reperfusion (modified thrombolysis in cerebral infarction grade 2c/3). Poor outcome was defined as a modified Rankin scale score of 3-6 at 90 days. The ischemic core infarct territories were classified into the cortical and subcortical areas. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used in this study. RESULTS: Of the 65 patients analyzed, 38 (58.5%) had a poor outcome. Multivariable logistic analysis showed that the subcortical infarcts (OR 11.75; 95% CI 1.79-77.32; P = 0.010) and their volume (OR 1.17; 95% CI 1.04-1.32; P = 0.011) were independently associated with poor outcome. The ROC curve indicated the capacity of the subcortical infarct involvement (areas under the curve (AUC) = 0.65; 95% CI, 0.53-0.77, P < 0.001) and subcortical infarct volume (AUC = 0.72; 95% CI, 0.60-0.83, P < 0.001) in predicting poor outcome accurately. CONCLUSION: Subcortical infarcts and their volume on admission CTP are associated with poor outcome after excellent reperfusion in late time windows, rather than cortical infarcts.

MAP4K4 promotes ovarian cancer metastasis through diminishing ADAM10-dependent N-cadherin cleavage.

Peritoneal metastasis is a key feature of advanced ovarian cancer, but the critical protein required for ovarian cancer metastasis and progression is yet to be defined. Thus, an unbiased high throughput and in-depth study is warranted to unmask the mechanism. Transcriptomic sequencing of paired primary ovarian tumors and metastases unveiled that MAP4K4, a serine/threonine kinase belongs to the Ste20 family of kinases, was highly expressed in metastatic sites. Increased MAP4K4 expression in metastasis was further validated in other independent patients, with higher MAP4K4 expression associated with poorer survival, higher level of CA125 and more advanced FIGO stage. Down regulation of MAP4K4 inhibited cancer cell adhesion, migration, and invasion. Notably, MAP4K4 was found to stabilize N-cadherin. Further results showed that MAP4K4 mediated phosphorylation of ADAM10 at Ser436 results in suppression of N-cadherin cleavage by ADAM10, leading to N-cadherin stabilization. Pharmacologic inhibition of MAP4K4 abrogated peritoneal metastases. Overall, our data reveal MAP4K4 as a significant promoter in ovarian cancer metastasis. Targeting MAP4K4 may be a potential therapeutic approach for ovarian cancer patients.

Low-dose BPA and its substitute BPS promote ovarian cancer cell stemness via a non-canonical PINK1/p53 mitophagic signaling.

The environmental toxicity of bisphenol A (BPA) and its analog like bisphenol S (BPS) have drawn wide attention, but their roles in cancer progression remain controversial. Here, we investigated the effect of BPA/BPS on the development of ovarian cancer. Human internal BPA/BPS exposure levels were analyzed from NHANES 2013-2016 data. We treated human ovarian cancer cells with 0-1000 nM BPA/BPS and found that 100 nM BPA/BPS treatment significantly increased Cancer Stem Cell (CSC) markers expression including OCT4, NANOG and SOX2. Cancer cell stemness evaluation induced by BPA/BPS was notably attenuated by the knockdown of PINK1 or Mdivi-1 treatment. The activation of PINK1 initiated mitophagy by inhibiting p-p53 nuclear translocation in a non-canonical manner. In vivo studies validated that BPA/BPS-exposed mice have higher tumor metastasis incidence compared with the control group, while mitophagy inhibition blocked such a promotion effect. In addition, CSC markers such as SOX2 had been found to be overexpressed in the tumor tissues of BPA/BPS exposure group. Taken together, the findings herein first provide the evidence that environmentally relevant BPA/BPS exposure could enhance ovarian cancer cell stemness through a non-canonical PINK1/p53 mitophagic pathway, raising concerns about the potential population hazards of BPA and other bisphenol analogs.

Alberta Stroke Program Early CT Score and collateral status predict target mismatch in large vessel occlusion with delayed time windows.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) and collateral score (CS) are two readily available imaging metrics for the evaluation of acute ischemic stroke (AIS) with large vessel occlusion (LVO). OBJECTIVE: To investigate the predictive value of the ASPECTS combined with CS in detecting patients with CT perfusion (CTP) target mismatch in delayed time windows. METHODS: One hundred and sixty-four patients with LVO-AIS were included. ASPECTS was assessed on non-contrast CT (NCCT). CS was evaluated on single-phase CT angiography (sCTA). Target mismatch was defined as a CTP core volume ≤70 mL, mismatch ratio ≥1.8, and absolute mismatch volume ≥15 mL. Spearman correlation analysis and receiver operating characteristic curve analyses were performed. RESULTS: The median NCCT ASPECTS of the 164 patients was 8 (IQR 6-9), median sCTA-CS was 2 (IQR 1-2), and median CTP core volume was 8 mL (IQR 0-29.5). There was a strong correlation between NCCT ASPECTS and CTP core volume (rs=-0.756, p<0.0001) and a moderate correlation between the sCTA-CS and CTP core volume (rs=-0.450, p<0.0001). Integrating NCCT ASPECTS and sCTA-CS provided a higher area under the curve (AUC) for predicting target mismatch (AUC=0.882; sensitivity, 89.1%; specificity, 77.8%; p<0.001). CONCLUSIONS: NCCT ASPECTS had a strong correlation with CTP core volumes in patients with LVO-AIS in delayed time windows. Combining NCCT ASPECTS with sCTA-CS resulted in a more accurate prediction of target mismatch. If a CTP scan is not available, NCCT ASPECTS combined with sCTA-CS may guide clinicians in making treatment decisions.

Predictors of Futile Recanalization in Patients with Intracranial Atherosclerosis-Related Stroke Undergoing Endovascular Treatment.

OBJECTIVE: The predictors of futile recanalization in patients with intracranial atherosclerosis (ICAS)-related stroke are not understood. This study aimed to identify the predictors of futile recanalization after endovascular treatment (EVT) in patients who experience an acute stroke caused by ICAS-related occlusion. METHODS: We retrospectively reviewed the data of patients with ICAS-related stroke who underwent EVT from January 2018 to July 2021. Futile recanalization was defined as functional dependence (modified Rankin scale 3-6) despite successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2 b/3). Multivariate logistic regression analysis was used to determine the risk factors associated with futile recanalization. The receiver operating characteristic curve was used to examine the predictive value of the risk prediction model for futile recanalization. RESULTS: Of the 87 patients enrolled, futile recanalization was observed in 32 (36.8%). Multivariate logistic analysis showed that older age (OR, 1.05; 95% CI, 1.01-1.10; P = 0.026), a higher National Institutes of Health Stroke Scale (NIHSS) score on admission (OR, 1.25; 95% CI, 1.08-1.45; P = 0.003), and poor collaterals (OR, 5.49; 95% CI, 1.70-17.79; P = 0.004) were independently associated with futile recanalization after EVT in patients with ICAS-related stroke. The receiver operating characteristic curve showed that the model in combination with age, admission NIHSS score, and collateral status could accurately predict futile recanalization in these patients (areas under the curve, 0.85; 95% CI, 0.76-0.92; P < 0.001). CONCLUSIONS: Older age, higher NIHSS score on admission, and poor collaterals are predictors of futile recanalization in patients with ICAS-related stroke.

Predictors of futile recanalization in patients with acute ischemic stroke undergoing mechanical thrombectomy in late time windows.

Background and purpose: Futile recanalization (FR), defined as functional dependence despite successful reperfusion, is common in patients who experience an acute stroke after thrombectomy. We aimed to determine the predictors of FR in patients who underwent thrombectomy in late time windows (6 h or more after symptom onset). Methods: This retrospective review included patients who underwent thrombectomy for acute anterior circulation large vessel occlusion from October 2019 to June 2021. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b/3. Functional dependence at 90 days was defined as a modified Rankin scale score of 3-6. Multivariate analysis and a receiver operating characteristic (ROC) curve were used to identify the predictors of FR in patients treated in delayed time windows. Results: Of the 99 patients included, FR was observed in 51 (51.5%). In the multivariate analysis, older age (OR, 1.12; 95% CI, 1.04-1.22; P = 0.005), female sex (OR, 3.79; 95% CI, 1.08-13.40; P = 0.038), a higher National Institutes of Health Stroke Score (NIHSS) score upon admission (OR, 1.11; 95% CI, 1.02-1.22; P = 0.023), and an increased number of passes per procedure (OR, 2.07; 95% CI, 1.11-3.86; P = 0.023) were independently associated with FR after thrombectomy. The ROC curve indicated that the model that combined age, female sex, baseline NIHSS score, and the number of passes per procedure (area under the curve, 0.84; 95% CI, 0.75-0.90, P < 0.001) was able to predict FR accurately. Conclusions: Older age, female sex, higher NIHSS score upon admission, and an increased number of passes per procedure were independent predictors of FR in patients who experienced acute ischemic strokes after thrombectomy in late time windows.

Initial and mid-term results of LEO Baby stent-assisted coiling of intracranial aneurysms located in small arteries: A single-center experience with 131 consecutive patients.

Background and purpose: Low-profile intracranial stents such as the LEO Baby stents are considered to be advantageous for the treatment of intracranial aneurysms originating from small arteries. This study aimed to evaluate the initial and mid-term clinical and angiographic results of LEO Baby stents in stent-assisted coiling of intracranial aneurysms with small parent arteries (<2.5 mm). Methods: We performed a retrospective study to identify 131 patients with aneurysms arising from small parent arteries treated with Leo Baby stent-assisted coiling in a single institution between October 2018 and June 2021. We assessed the immediate and progressive aneurysm occlusion rates, procedure-related complications, and clinical outcomes. Results: A total of 131 patients with 135 aneurysms were identified, including 65 (48.1%) cases of acutely ruptured aneurysms. Technical success was achieved in all cases (100%). The immediate angiography showed complete occlusion in 111 aneurysms (82.2%), neck remnants in 19 (14.1%), and residual sac in 5 (3.7%). Procedure-related complications occurred in 14 cases (10.3%), including 13 (9.6%) thromboembolic complications and 1 (0.7%) hemorrhagic complication. Six-month follow-up angiography was achieved in 106 (78.5%) aneurysms, which showed complete occlusion in 102 (96.2%) aneurysms, neck remnants in 2 (1.9%), and residual sac in 2 (1.9%). Clinical follow-up was available in all patients with a median duration of 6.8 months, and favorable clinical outcomes (modified Rankin Scale score: 0-2) reached 91.6%. The mortality rate was 4.6%. Conclusion: Our results demonstrate that stent-assisted coiling of intracranial aneurysms located on small arteries using LEO Baby stents is technically feasible, highly effective, and has midterm durability in aneurysmal occlusion.

Identification of metastasis-related long non-coding RNAs in lung cancer through a novel tumor mesenchymal score.

Long non-coding RNAs (lncRNAs) have been proven to play critical roles in epithelial-mesenchymal transition (EMT) and metastasis of lung cancer. However, the biological functions and related mechanisms of lncRNAs are unclear. In addition, the EMT-based prognosis prediction in lung cancer still lacks investigation. Here, we established the methodology of identifying critical metastasis-related lncRNAs using comprehensive datasets of cancer transcriptome, genome and epigenome, and also provided tools for prognosis prediction in lung cancer. Initially, important mesenchymal marker genes were identified to compose the tumor mesenchymal score, which predicted patient prognosis in lung cancer, especially lung adenocarcinoma (LUAD). The score was also correlated with several crucial biological and physiological processes, such as tumor immune and hypoxia. Based on the score, lung cancer patients was classified into epithelial and mesenchymal subtypes, and lncRNAs which exhibited expressional dysregulation, promotor methylation alteration and copy number variation between the two subtypes in LUAD were identified and underwent further prognostic analyses. Finally, we identified 14 lncRNAs as EMT-related and significant biomarkers in prognosis prediction of LUAD. As validation, lncRNA RBPMS-AS1 was proven to be co-expressed with epithelial biomarkers, suppressive for A549 cell migration, invasion and EMT, and also significantly associated with better outcomes of LUAD patients, suggesting the potential of RBPMS-AS1 to serve as a lncRNA epithelial biomarker in metastasis of LUAD. Based on the identified lncRNAs, an EMT-linked lncRNA prognostic signature was further established. Taken together, our study provides robust predictive tools, potential lncRNA targets and feasible screening strategies for future study of lung cancer metastasis.

Balloon Angioplasty Combined with Tirofiban as a First-Line Rescue Treatment After Failed Mechanical Thrombectomy for Middle Cerebral Artery Occlusion with Underlying Atherosclerosis.

OBJECTIVE: The standard rescue modality for patients with intracranial atherosclerotic stenosis after failed mechanical thrombectomy (MT) is not well established. We evaluated the safety and efficacy of balloon dilation in combination with tirofiban as the first-line salvage therapy when MT failed in these patients. METHODS: We retrospectively analyzed the records of 47 patients admitted between January 2018 and June 2021, with middle cerebral artery atherosclerotic occlusion, who underwent balloon angioplasty in combination with tirofiban as the first-line salvage therapy after the failure of MT. The recanalization outcome, procedure-related complications, symptomatic intracranial hemorrhage, and functional outcome at 90 days were reviewed. RESULTS: Recanalization with a modified Thrombolysis in Cerebral Infarction grade of 2b-3 was achieved in 41 (87.2%) of the 47 patients. Acute stents were deployed in another 6 patients who did not achieve successful re-perfusion after balloon angioplasty. Successful recanalization was achieved in 3 of them. One patient (2.1%, 1/47) experienced re-occlusion several days later due to the withdrawal of antiplatelet therapy for parenchymal hematoma. Seven patients (14.9%, 7/47) underwent stent angioplasty in the stable stage (range: 1-2 months) because severe residual stenosis was detected on follow-up imaging. There was only one event of periprocedural complication, namely ectopic migration of emboli. The good functional outcome rate was 55.3% (26/47), without the events of symptomatic intracranial hemorrhage and mortality. CONCLUSIONS: Balloon angioplasty in combination with tirofiban is safe and effective for middle cerebral artery atherosclerotic occlusion after the failure of MT.

Direct visualization of floppy two-dimensional DNA origami using cryogenic electron microscopy.

Two-dimensional (2D) DNA origami that is capable of self-assembling into complex 2D and 3D geometries pave the way for a bottom-up synthesis for various applications in nano/biotechnology. Here, we directly visualized the aqueous structure of 2D DNA origami cross-tiles and their assemblies using cryogenic electron microscopy. We uncovered flexible arms in cross-tile monomers and designated inter-tile folding. In addition, we observed the formation of clusters and stacks of DNA cross-tiles in solution, which could potentially affect the interaction and assembly of DNA origami. Finally, we quantitatively evaluated the flexibility of DNA origami in solution using finite element analysis. Our discovery has laid the foundation for investigating the dynamic structures of 2D DNA origami assemblies in solution, providing insights regarding the self-assembly and self-replication mechanisms of 2D DNA origami.

Stent-assisted coiling of unruptured paraclinoid aneurysms with wide neck or unfavorable dome-to-neck ratio: Results of ventral wall vs dorsal wall with propensity score matching analysis.

OBJECTIVE: This study aimed to evaluate the clinical safety and efficacy of stent-assisted coil embolization of unruptured wide-necked paraclinoid aneurysms based on the projection distribution. METHODS: Between November 2015 and September 2020, 267 unruptured paraclinod aneurysms in 236 patients were identified with a wide neck or unfavorable dome-to-neck ratio and treated with stent-assisted coiling technique. The classification of this segment aneurysms was simplified to the dorsal group (located on the anterior wall) and ventral group (Non-dorsal). Following propensity score matching analysis, the clinical and radiographic data were compared between the two groups. RESULTS: Among 267 aneurysms, 186 were located on the ventral wall and 81 were on the dorsal wall. Dorsal wall aneurysms had a larger size (p < .001), wider neck (p = .001), and higher dome-to-neck ratio (p = .023) compared with ventral wall aneurysms. Propensity score-matched analysis found that dorsal group had a significantly higher likelihood of unfavorable results in immediate (residual sac, 39.4% vs. 18.2%, p = .007) and follow-up angiography (residual sac, 14.8% vs. 1.9%, p = .037) compared with ventral group, with significant difference in recurrence rates (9.3% vs. 0%, p = .028). The rates of procedure-related complications were not significantly different, but one thromboembolic event occurred in the dorsal group with clinical deterioration. CONCLUSIONS: Traditional stent-assisted coiling can be given preference in paraclinoid aneurysms located on the ventral wall. The relatively high rate of recurrence in dorsal wall aneurysms with stent assistance may require other treatment options.

The ethanolic extract of Artemisia anomala exerts anti-inflammatory effects via inhibition of NLRP3 inflammasome.

BACKGROUND: Artemisia anomala S. Moore (Compositae), known as "Nan-Liu-Ji-Nu" in traditional Chinese medicine (TCM), has been used to treat many inflammatory diseases, including enteritis, acute icteric hepatitis, rheumatism, toothache, tonsillitis, and chronic bronchitis, for centuries. Our preliminary studies have demonstrated that the ethanolic extract of A. anomala (EAA) might be with the potential of inhibiting the activation of the NLRP3 inflammasome. However, the anti-inflammatory activity of EAA based on NLRP3 inflammasome inhibition is still unclear. PURPOSE: This work aimed to elucidate the anti-inflammatory mechanism of EAA by inhibiting NLRP3 inflammasome activation. METHODS: Lipopolysaccharide (LPS)-primed bone marrow-derived macrophages (BMDMs) were used to evaluate the inhibitory effects on NLRP3 inflammasome activation. The level of IL-1ß was determined by ELISA. The expression levels of IL-1ß, caspase-1, NLRP3, and ASC were assayed using western blot analysis. ASC oligomerization and speck formation were detected by immunofluorescence microscopy. The measurements of intracellular chloride and potassium were conducted using N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) probe assay and inductively coupled plasma-optical emission spectrometry (ICP-OES), respectively. Mitochondrial reactive oxygen species (mtROS) were examined using the MitoSOX method. Acridine orange (AO) staining was used to detect the permeability of the lysosomal membrane. A DSS-induced ulcerative colitis model was established to evaluate the anti-inflammatory effects of EAA in vivo. Finally, high-performance liquid chromatography (HPLC) was employed to identify and quantify the major constituents of EAA. RESULTS: In BMDMs, EAA significantly inhibited the release of IL-1ß induced by LPS. The mechanistic study revealed that EAA inhibited NLRP3 inflammasome activation by blocking the oligomerization of ASC and suppressed the LPS-induced priming step. Furthermore, EAA protected lysosomes by inhibiting the TAK1-JNK pathway, thereby inhibiting the assembly of downstream NLRP3 inflammasome and the production of IL-1ß. In addition, EAA exerted potent protective effects in an ulcerative colitis model by decreasing the content of colonic IL-1ß and alleviating the process of ulcerative colitis. HPLC analysis identified eight main components of EAA, including isofraxidin (1), quercetin-7-O-ß-D-glucopyranoside (2), apigenin-7-O-ß-D-glucopyranoside (3), 7-methoxycoumarin (4), quercetin (5), luteolin (6), kaempferol (7), and eupatorin (8), Of these compounds, quercetin and kaempferol were found to be the most potent ingredients. CONCLUSION: These findings collectively reveal that EAA exerts anti-inflammatory effects by both suppressing the NLRP3 priming step and protecting lysosomes to inhibit NLRP3 inflammasome activation, suggesting that this traditional herbal medicine might be used to treat NLRP3-driven inflammatory diseases.