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Perfluorobutane sulfonate (PFBS), a chemical compound within the group of per- and polyfluoroalkyl substances (PFAS), has been utilized as an alternative to perfluorooctane sulfonate (PFOS) recently. Previous research has indicated that PFBS might be linked to a range of health concerns. However, the potential impacts of environmentally relevant concentrations of PFBS (25 nM) on aging as well as the underlying mechanisms remained largely unexplored. In this study, we investigated the impact of PFBS exposure on aging and the associated mechanisms in Caenorhabditis elegans. Our findings indicated that exposure to PFBS impaired healthspan of C. elegans. Through bioinformatic screening analyses, we identified that the dysfunctions of pink-1 mediated mitophagy might play a critical role in PFBS induced aging. The results furtherly revealed that PFBS exposure led to elevated levels of reactive oxygen species (ROS) and mitophagy impairment through downregulating pink-1/pdr-1 pathway. Furthermore, the mitophagy agonist Urolithin A (UA) effectively reversed PFBS-induced mitophagy dysfunction and enhanced healthspan in C. elegans. Taken together, our study suggested that exposure to environmentally relevant concentrations of PFBS could accelerate aging by downregulating the pink-1 mediated mitophagy. Promoting mitophagy within cells could be a promising therapeutic strategy for delaying PFBS-induced aging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024 Ni et al.)

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.

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.

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., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2023. The Author(s).)

Benzo[a]pyrene (BaP) is commonly found in the environment as a result of incomplete combustion of organic materials and cigarette smoke. Epidemiological studies have consistently suggested that elderly smokers are at higher risk for small cell lung cancer (SCLC), with risks and clinical stages increasing with the intensity and duration of smoking. However, the underlying mechanism remains insufficiently investigated. Here, we established a positive correlation between smoking and BaP metabolite 3-hydroxybenzo[a]pyrene (3OH-BaP) in urine. The pooled standardized mean difference of urinary 3OH-BaP concentration for smokers versus nonsmokers was 5.18 (95 % CI 2.86-7.50). Clinical data suggested that smoking led to more lymph node metastasis, higher pathological N-stage, and worse overall survival in SCLC patients. We identified 75 genes that participate in BaP-associated cancer stemness of SCLC from Comparative Toxicogenomics Database and validated the expression of these candidate genes in SCLC patient samples. Protein kinase cAMP-activated catalytic subunit alpha (PRKACA) was found to be most upregulated in SCLC patients and in vitro experiments indicated that long-term exposure of SCLC cells to BaP, at the concentration equivalent to those detected in blood, increased PKA protein level. Further investigation revealed that PKA could directly interact with SOX2 and protect SOX2 from COP1-mediated ubiquitination and degradation. Upregulated SOX2 then contributed to the stemness and metastasis of SCLC cells while inhibition of aryl hydrocarbon receptor (AhR) signaling pathway abolished BaP induced PKA expression and downstream PKA/SOX2 axis. Our findings firstly pinpoint BaP exposure as a high-risk factor for SCLC and worse outcomes in patients, with the underlying mechanism being the activation of cancer stemness of SCLC via the AhR/PKA/SOX2 axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

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.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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 (r s =-0.756, p<0.0001) and a moderate correlation between the sCTA-CS and CTP core volume (r s =-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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: Declaration of Competing Interest We declare we have no actual or potential competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: Pseudo-occlusion of the cervical internal carotid artery (cICA) refers to an absence of intraluminal contrast on computed tomography angiography (CTA), while the artery is patent on digital subtraction angiography during endovascular thrombectomy. We aimed to compare the outcomes between the cICA pseudo-occlusion and true occlusion after thrombectomy., Methods: We retrospectively analyzed patients with apparent cICA occlusion on CTA who underwent thrombectomy between January 2016 and August 2021, and divided them into the pseudo-occlusion and true occlusion groups based on angiographic exploration. Recanalization failure was defined as a modified Thrombolysis in Cerebral Infarction score of 0-2a. Poor outcome was defined as a 90-day modified Rankin Scale score of 3-6. Propensity score matching was performed to compare the outcomes. Sensitivity analysis using multivariate-adjusted regression in the original cohort was conducted to test the robustness of the findings., Results: Of the 146 patients included, 79 patients (54.1%) had cICA pseudo-occlusion and 67 patients (45.9%) had true occlusion. Following 1:1 propensity score-matched analysis, patients with pseudo-occlusion had an increased likelihood of recanalization failure (OR, 3.18; 95% CI, 1.06-9.59; P = 0.040) and poor outcome (OR, 2.80; 95% CI, 1.07-7.30; P = 0.035) compared with patients with true occlusion. Sensitivity analysis showed that cICA pseudo-occlusion remained independently associated with recanalization failure (OR, 2.55; 95% CI, 1.07-6.09; P = 0.036) and poor outcome (OR, 2.48; 95% CI, 1.08-5.67; P = 0.032)., Conclusions: Patients with cICA pseudo-occlusion on CTA treated with thrombectomy had an increased risk of reperfusion failure and poor outcome compared with true occlusion patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ni, Yang, Jia, Shi, Liu and Zhao.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ni, Liu, Hang, Jia, Cao, Shi, Liu and Zhao.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Ni, Li, Jia, Cao, Shi, Zhao and Liu.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

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-1β was determined by ELISA. The expression levels of IL-1β, 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-1β 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-1β. In addition, EAA exerted potent protective effects in an ulcerative colitis model by decreasing the content of colonic IL-1β and alleviating the process of ulcerative colitis. HPLC analysis identified eight main components of EAA, including isofraxidin (1), quercetin-7-O-β-D-glucopyranoside (2), apigenin-7-O-β-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., (Copyright © 2022. Published by Elsevier GmbH.)

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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors present no competing interests., (© 2022 The Author(s).)

Background: To determine the risk factors for intracranial hematoma (ICH) development following ruptured anterior communicating artery (AcomA) aneurysms and to determine prognostic factors associated with unfavorable outcomes after coiling first., Methods: From March 2014 to February 2020, 235 patients with ruptured AcomA aneurysms underwent endovascular treatment in our department. The clinical and radiographic conditions were collected retrospectively. Modified Rankin Scale (mRS) scores of ≤ 2 were accepted as favorable outcomes. Univariate and multivariate logistic regressions were performed to identify significant factors contributing to the incidence of ICHs and to unfavorable outcomes., Results: Of these 235 patients, 68 had additional ICHs. A posterior orientation of ruptured AcomA aneurysms was the independent variable associated with the incidence of ICHs (OR 3.675; p<0.001). Furthermore, having preoperative Hunt-Hess grades Ⅳ-Ⅴ was an independent variable associated with unfavorable outcomes for ICH patients (OR 80.000; p<0.001). Among the 68 patients with ICHs, 40% (27/68) had Hunt-Hess grades IV-V. Four percent of patients (3/68) underwent surgical hematoma evacuation after the coiling procedure and 15% of the patients (10/68) underwent external ventricular drainage. A favorable outcome was achieved in 72% (49/68) of patients with ruptured AcomA aneurysms. The mortality rate was 21% (14/68) at 6 months., Conclusion: A posterior orientation of ruptured AcomA aneurysms was associated with the incidence of ICHs. Coiling first with surgical management if necessary seems to be an acceptable treatment for ruptured AcomA aneurysms with ICHs. The clinical outcome was associated with the clinical neurological status on admission., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022. The Author(s).)

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., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Although mutations of genes are crucial events in tumorigenesis and development, the association between gene mutations and lung cancer metastasis is still largely unknown. The goal of this study is to identify driver and novel genes associated with non-small cell lung cancer (NSCLC) metastasis. Candidate genes were identified using a novel comprehensive analysis, which was based on bioinformatics technology and meta-analysis. Firstly, EGFR, KRAS, ALK, TP53, BRAF and PIK3CA were identified as candidate driver genes. Further meta-analysis identified that EGFR (Pooled OR 1.33, 95% CI 1.19, 1.50; P < .001) and ALK (Pooled OR 1.52, 95% CI 1.22, 1.89; P < .001) mutations were associated with distant metastasis of NSCLC. Besides, ALK (Pooled OR 2.40, 95% CI 1.71, 3.38; P < .001) mutation was associated with lymph node metastasis of NSCLC. In addition, thirteen novel gene mutations were identified to be correlated with NSCLC metastasis, including SMARCA1, GGCX, KIF24, LRRK1, LILRA4, OR2T10, EDNRB, NR1H4, ARID4A, PRKCI, PABPC5, ACAN and TLN1. Furthermore, elevated mRNA expression level of SMARCA1 and EDNRB was associated with poor overall survival in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively. Additionally, pathway and protein-protein interactions network analyses found the two genes were correlated with epithelial-mesenchymal transition process. In conclusion, mutations of EGFR and ALK were significantly correlated with NSCLC metastasis. In addition, thirteen novel genes were identified to be associated with NSCLC metastasis, especially SMARCA1 in LUAD and EDNRB in LUSC., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Objective: This study aimed to investigate the safety and efficacy of endovascular embolization for very small ruptured anterior communicating artery (AcomA) aneurysms., Methods: From August 2015 to June 2020, 81 patients with very small (≤3 mm) ruptured AcomA aneurysms treated endovascularly were enrolled in this study. Clinical and radiographic data were analyzed retrospectively, including the aneurysm occlusion rate, complications, and clinical outcome., Results: Among 81 patients, simple coiling embolization was performed in 52 cases and stent-assisted embolization in 29 cases. Immediate angiography demonstrated complete occlusion in 59 (72.8%) aneurysms, residual neck in 20 (24.7%) aneurysms, and residual lumen in 2 (2.5%). Procedure-related complications rate was 2.5% (2 of 81), all of which were transient thromboembolic events. Angiographic follow-up outcomes of 60 patients (mean: 6.8 ± 3.2 months) revealed complete occlusion in 91.7% (55 of 60), with recurrence in 1 patient. The mean clinical follow-up time was 22.6 ± 11.4 months and good prognosis rates (6-month modified Rankin Scale score: 0-2) reached 90.2% (73 of 81). The differences in aneurysm occlusion and procedure-related complications between the simple coiling group and the stent-assisted coiling group were not statistically significant., Conclusions: Coiling with or without stent-assisted technique for the treatment of very small ruptured AcomA aneurysms was safe and effective., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Compared with open surgery, video-assisted thoracic surgery (VATS) has innovated the concept of the minimally invasive approach for non-small cell lung cancer (NSCLC) patients in past decades. This present study aimed to compare the perioperative and lymph node dissection outcomes between VATS lobectomy and open lobectomy for pathological stage T1 (pT1) NSCLC patients from both surgical and oncologic perspectives., Methods: This was a retrospective multicenter study. Patients who underwent surgical resection for pT1 NSCLC between January 2014 and September 2017 were retrospectively reviewed from 10 thoracic surgery centers in China. Perioperative and lymph node dissection outcomes of pT1 NSCLC patients who accepted VATS or open lobectomies were compared by propensity score matching (PSM) analysis., Results: Of the 11,360 patients who underwent surgery for pT1 NSCLC, 7,726 were enrolled based on the selection criteria, including 1,222 cases of open lobectomies and 6,504 cases of VATS lobectomies. PSM resulted in 1,184 cases of open lobectomies and 1,184 cases of VATS lobectomies being well matched by common prognostic variables, including age, sex, and surgical side. VATS lobectomy led to better perioperative outcomes, including less blood loss (133.5±200.1 vs. 233.3±318.4, P<0.001), lower blood transfusion rate (2.4% vs. 6.4%, P<0.001), shorter postoperative hospital stay (8.6±5.7 vs. 10.1±5.1, P<0.001), less chest drainage volume (1,109.5±854.0 vs. 1,324.1±948.8, P<0.001), and less postoperative complications (4.9% vs. 8.2%, P<0.001). However, open lobectomy had better lymph node dissection outcomes than VATS, with increased lymph node dissection numbers (16.1±9.4 vs. 13.7±7.7, P<0.001) and more positive lymph nodes being dissected (1.5±3.9 vs. 1.1±2.5, P=0.002). Compared with VATS, open lobectomy harvested more lymph node stations (5.5±1.9 vs. 5.2±1.8, P=0.001), including more pathological N2 (pN2) lymph node stations (3.4±1.4 vs. 3.1±1.3, P<0.001)., Conclusions: VATS lobectomy was associated with better perioperative outcomes, such as less blood loss, lower blood transfusion rate, shorter postoperative hospital stay, less chest drainage volume and less postoperative complications. Open lobectomy has improved lymph node dissection outcomes, as more lymph nodes and positive lymph nodes were dissected for pT1 NSCLC patients during surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1132). The authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

The study aimed at determining the effect of different zinc (Zn) supplementation forms on Zn accumulation, activities of Zn-containing enzymes, gene expression of metallothionein (MT), and Zn transporters in piglets. Eighteen piglets were randomly divided into three groups: (a) a basal diet supplemented with 150 mg/kg Zn from Zn methionine (Zn-Met) in the feed (Zn-Met group), (b) a basal diet supplemented with 150 mg/kg Zn from Zn sulfate (ZnSO 4 ) in the feed (ZnSO 4 , feed group), and (c) a basal diet supplemented with the same dose of Zn as in ZnSO4, feed group but in water (ZnSO 4 , water group). The results showed that Zn-Met added in feed and ZnSO 4 dissolved in drinking water significantly improved ( p < 0.05) the Zn concentration in liver and jejunum and the apparent digestibility of Zn in comparison with the ZnSO 4 added in feed. In addition, dietary Zn supplementation as Zn-Met significantly increased ( p < 0.05) the activity of alkaline phosphatase (AKP) in the jejunum of piglets in comparison with the ZnSO 4 , feed group. Furthermore, the Zn-Met and ZnSO 4 , water groups showed an improved total superoxide dismutase activity (T-SOD) in the ileum as compared to the ZnSO 4 , feed group. Meanwhile, the qPCR and western blot results showed that Zn-Met and ZnSO 4 dissolved in drinking water increased the expression of MT in the jejunum in comparison with the ZnSO 4 added in the piglets' feed. However, different Zn supplementation forms had no effect on the mRNA expressions of Zip4 and ZnT1 transporters. In conclusion, Zn-Met added in feed and ZnSO 4 dissolved in drinking water had higher bioavailability in piglets.

Six new biphenyl-type neolignans (1-6), and eighteen known compounds (7-24) were isolated from the EtOH extract of Magnolia officinalis. Their structures were determined by 1D and 2D NMR, and by HRMS. The anti-tumor activities of the isolated compounds were evaluated on HepG2, HCT-116, H1975 and HUVEC cell lines. Among the isolated compounds, nine compounds (3, 5, 7, 8, 12, 14, 20, 22, and 24) showed moderate cytotoxicities, and compound 23 showed the best cytotoxicity with IC 50 value lower than 10 μM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Eight new flavonoids, including two β-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 (IC 50 : 1.3 μM) against nigericin-induced IL-1β 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-1β 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-1β 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.

Graphene has demonstrated great potential in new-generation electronic applications due to its unique electronic properties such as large carrier Fermi velocity, ultrahigh carrier mobility, and high material stability. Interestingly, the electronic structures can be further engineered in multilayer graphene by the introduction of a twist angle between different layers to create van Hove singularities (vHSs) at adjustable binding energy. In this work, using angle-resolved photoemission spectroscopy with sub-micrometer spatial resolution, the band structures and their evolution are systematically studied with twist angle in bilayer and trilayer graphene sheets. A doping effect is directly observed in graphene multilayer system as well as vHSs in bilayer graphene over a wide range of twist angles (from 5° to 31°) with wide tunable energy range over 2 eV. In addition, the formation of multiple vHSs (at different binding energies) is also observed in trilayer graphene. The large tuning range of vHS binding energy in twisted multilayer graphene provides a promising material base for optoelectrical applications with broadband wavelength selectivity from the infrared to the ultraviolet regime, as demonstrated by an example application of wavelength selective photodetector., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)