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.

Mutations in artificial self-replicating tiles: A step toward Darwinian evolution.

Artificial self-replication and exponential growth holds the promise of gaining a better understanding of fundamental processes in nature but also of evolving new materials and devices with useful properties. A system of DNA origami dimers has been shown to exhibit exponential growth and selection. Here we introduce mutation and growth advantages to study the possibility of Darwinian-like evolution. We seed and grow one dimer species, AB, from A and B monomers that doubles in each cycle. A similar species from C and D monomers can replicate at a controlled growth rate of two or four per cycle but is unseeded. Introducing a small mutation rate so that AB parents infrequently template CD offspring we show experimentally that the CD species can take over the system in approximately six generations in an advantageous environment. This demonstration opens the door to the use of evolution in materials design.

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.

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.

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.

A novel lncRNA lnc-PPRL promotes pterygium development by activating PI3K/PDK1 signaling pathway.

A sight threatening, pterygium is a common proliferative and degenerative disease of the ocular surface. LncRNAs have been widely studied in the occurrence and development of various diseases, however, the study of lncRNAs in pterygium has just relatively lacking. In the present study, we performed the high-throughput RNA sequencing (HTS) technology to identify differentially expressed lncRNAs in pterygium. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to forecast the regulatory and functional role of lncRNAs in pterygium. Notably, we identified a novel lncRNA, LOC102724238, which we named pterygium positively-related lncRNA (lnc-PPRL), was up-regulated in pterygium. Lnc-PPRL showed to be preferentially accumulated in cytoplasm, and it can promote cell proliferation, migration and invasion of human pterygium epithelium cells (hPECs). Further study of underlying mechanisms demonstrated that lnc-PPRL may exert its biological effect by activating canonical PI3K/PDK1 pathway, and subsequently promoting the activation of Akt/mTOR signaling pathway and its downstream effectors. Interestingly, lnc-PPRL was also proved to influence YAP nuclear localization. Taken together, our study firstly suggested that the "big molecule" lnc-PPRL have potential as a novel therapeutic target for the prevention and treatment of pterygium.

Endovascular thrombectomy for acute ischemic stroke in elderly patients with atrial fibrillation.

BACKGROUND: To assess the clinical outcomes after endovascular thrombectomy (EVT) in elderly large vessel occlusion (LVO)-related acute ischemic stroke (AIS) patients with atrial fibrillation (AF). METHODS: Between January 2019 and December 2020, consecutive AF patients who received EVT due to anterior-circulation stroke were enrolled. The primary outcome was modified Rankin scale (mRS) score at 90 days. Secondary outcomes included all-cause mortality, the recanalization status after EVT (assessed using modified thrombolysis in cerebral infarction scale, mTICI) and any intracranial hemorrhage (ICH). A multivariate logistic regression model was performed to identify predictors of the functional outcome. RESULTS: A total of 148 eligible patients were finally enrolled. Among them, 42 were ≥ 80 years old. Compared to their younger counterparts, patients aged ≥80 years had lower likelihood of good functional outcome (mRS score 0-2) at 90 days (26.2% vs. 48.1%, P = 0.015), less satisfied recanalization (mTICI, 2b-3) (78.6% vs. 94.3%, P = 0.004) and higher all-cause mortality rate (35.7% vs. 14.2%, P = 0.003). A multivariable logistic regression analysis showed that age ≥ 80 years at baseline were the significant predictors for a poor functional outcome (OR: 3.72, 95% CI: 1.17-11.89, p = 0.027). Intravenous thrombolysis (IVT) prior to EVT and longer time intervals from onset of symptoms to EVT tended to be associated with poor functional outcome in patients ≥80 years old. CONCLUSIONS: Age ≥ 80 years was a significant predictor of unfavorable outcomes after EVT for AIS patients with AF. An increased risk of adverse events must be balanced against the benefit from EVT in elderly patients with AF.

Open-cell stent-assisted coiling for the treatment of paraclinoid aneurysms: traditional endovascular treatment is still not out of date.

PURPOSE: Before we enter the era of flow diverter stents (FDS), the standard stent-assisted coiling technique is a well-established treatment option for routine paraclinoid aneurysms. We assess the clinical safety and efficacy of stent-assisted coiling with open-cell stent in the treatment of paraclinoid aneurysms and evaluate the association between clinical factors and follow-up aneurysm occlusion. METHODS: The clinical and radiographic data of 110 consecutive patients with 122 paraclinoid aneurysms treated with open-cell stent between April 2015 and April 2019 were analyzed retrospectively at our center. We assessed the immediate and progressive occlusion rates, complications, and clinical outcome. Multivariate analysis was performed to investigate the risk factors of angiographic incomplete occlusion. RESULTS: Among 110 patients, stent-assisted coiling was successfully performed in all cases. Four (3.6%) thromboembolic events were reported during the procedure, which resulted in transient morbidity. Immediate angiography demonstrated complete occlusion in 64 (52.5%) aneurysms and no occlusion of ophthalmic artery. Angiographic follow-up at 6 months demonstrated an increase in the complete occlusion rate to 92.9%. No delayed in-stent stenosis was observed, and three aneurysms recurred. Clinical follow-up was completed in 102 patients (92.7%), and favorable outcomes were achieved in 101 (99%) patients at 6 months. Multivariate analysis showed that aneurysm size (p < 0.001) was associated with incomplete aneurysm occlusion at follow-up. CONCLUSION: Stent-assisted coil embolization with open-cell stents is safe and effective for the treatment of paraclinoid aneurysms and provides progressive occlusion without significant in-stent stenosis events.

Flavonoids with Inhibitory Effects on NLRP3 Inflammasome Activation from Millettia velutina.

Eight new flavonoids, including two ß-hydroxy/methoxychalcones, velutones A and B (1 and 2), two 1,3-diarylpropan-1-ols, velutols C and D (3 and 4), a dihydroxychalcone, velutone E (5), a chalcone, velutone F (6), a furanoflavanone, velutone G (7), and a furanoflavonol, velutone H (8), and 14 known compounds were isolated from Millettia velutina. Their structures were determined by high-resolution electrospray ionisation mass spectrometry (HR-ESIMS) and spectroscopic data analyses and time-dependent density functional theory electronic circular dichroism (TD-DFT-ECD) calculations. Among the isolated constituents, compound 6 exhibited the most potent inhibitory effect (IC50: 1.3 µM) against nigericin-induced IL-1ß release in THP-1 cells. The initial mechanism of action study revealed that compound 6 suppressed NLRP3 inflammasome activation via blocking ASC oligomerization without affecting the priming step, which subsequently inhibited caspase-1 activation and IL-1ß secretion. Most importantly, compound 6 exerted potent protective effects in the LPS-induced septic shock mice model by improving the survival rate of mice and suppressing serum IL-1ß release. These results demonstrated that compound 6 had the potential to be developed as a broad-spectrum NLRP3 inflammasome inhibitor for the treatment of NLRP3-related disease.

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.

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.

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.

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.

Dysfunctional circadian clock accelerates cancer metastasis by intestinal microbiota triggering accumulation of myeloid-derived suppressor cells.

Circadian homeostasis in mammals is a key intrinsic mechanism for responding to the external environment. However, the interplay between circadian rhythms and the tumor microenvironment (TME) and its influence on metastasis are still unclear. Here, in patients with colorectal cancer (CRC), disturbances of circadian rhythm and the accumulation of monocytes and granulocytes were closely related to metastasis. Moreover, dysregulation of circadian rhythm promoted lung metastasis of CRC by inducing the accumulation of myeloid-derived suppressor cells (MDSCs) and dysfunctional CD8+ T cells in the lungs of mice. Also, gut microbiota and its derived metabolite taurocholic acid (TCA) contributed to lung metastasis of CRC by triggering the accumulation of MDSCs in mice. Mechanistically, TCA promoted glycolysis of MDSCs epigenetically by enhancing mono-methylation of H3K4 of target genes and inhibited CHIP-mediated ubiquitination of PDL1. Our study links the biological clock with MDSCs in the TME through gut microbiota/metabolites in controlling the metastatic spread of CRC, uncovering a systemic mechanism for cancer metastasis.

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.

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.

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.

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.

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.