We examined functional outcomes of mechanical thrombectomy (MT) procedures following anterior circulation large vessel occlusion (ACLVO)-related acute ischemic strokes (AIS). Results were based on ...admission non-contrast computed tomography (NCCT) studies, using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) as standard metric.
Qualifying subjects were consecutive patients (N = 343) at a single center undergoing MT for ACLVO-related AIS. Each was grouped according to ASPECTS status on admission, determined from NCCT images by two physicians. Primary clinical endpoint was functional independence, assessed via modified Rankin Scale (mRS) at 90 days. Secondary endpoints were vessel recanalization (i.e., modified Thrombolysis in Cerebral Infarction mTICI score), symptomatic intracranial hemorrhage (sICH), and mortality.
In this study population (mean age, 63.6 ± 12.6 years; women, 30.3%; median baseline National Institute of Health Stroke Scale NIHSS score, 15.2 ± 4.5), patients were stratified by ASPECTS tier at presentation, either 0-5 (n = 50) or 6-10 (n = 293). Multivariate logistic regression showed a relation between ASPECTS values ≤ 5 and lesser chance of 90-day functional improvement (OR = 2.309, 95% confidence interval CI 1.012-5.271; p = 0.047), once adjusted for age, baseline NIHSS score, diabetes mellitus, HbA1c concentration, D-dimer level, occlusive location, numbers of device passes, and successful recanalization.
ASPECTS values ≤ 5 correspond with worse long-term functional improvement (mRS scores > 2) in patients undergoing MT for ACLVO-related AIS. Other independent determinants of functional outcomes after MT are age, baseline NIHSS score, HbA1c concentration, and successful recanalization.
Cerebral ischemia-reperfusion injury (CIRI) refers to a secondary brain injury that can occur when the blood supply to the ischemic brain tissue is restored. However, the mechanism underlying such ...injury remains elusive.
The 150 male C57 mice underwent middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h, Among them, 50 MCAO mice were further treated with Mitochondrial division inhibitor 1 (Mdivi-1) and 50 MCAO mice were further treated with N-acetylcysteine (NAC). SH-SY5Y cells were cultured in a low-glucose culture medium for 4 h under hypoxic conditions and then transferred to normal conditions for 12 h. Then, cerebral blood flow, mitochondrial structure, mitochondrial DNA (mtDNA) copy number, intracellular and mitochondrial reactive oxygen species (ROS), autophagic flux, aggresome and exosome expression profiles, cardiac tissue structure, mitochondrial length and cristae density, mtDNA and ROS content, as well as the expression of Drp1-Ser616/Drp1, RIP1/RIP3, LC3 II/LC3 I, TNF-α, IL-1β, etc., were detected under normal or Drp1 interference conditions.
The mtDNA content, ROS levels, and Drp1-Ser616/Drp1 were elevated by 2.2, 1.7 and 2.7 times after CIRI (P < 0.05). However, the high cytoplasmic LC3 II/I ratio and increased aggregation of p62 could be reversed by 44% and 88% by Drp1 short hairpin RNA (shRNA) (P < 0.05). The low fluorescence intensity of autophagic flux and the increased phosphorylation of RIP3 induced by CIRI could be attenuated by ROS scavenger, NAC (P < 0.05). RIP1/RIP3 inhibitor Necrostatin-1 (Nec-1) restored 75% to a low LC3 II/LC3 I ratio and enhanced 2 times to a high RFP-LC3 after Drp1 activation (P < 0.05). In addition, although CIRI-induced ROS production caused no considerable accumulation of autophagosomes (P > 0.05), it increased the packaging and extracellular secretion of exosomes containing p62 by 4 - 5 times, which could be decreased by Mdivi-1, Drp1 shRNA, and Nec-1 (P < 0.05). Furthermore, TNF-α and IL-1β increased in CIRI-derived exosomes could increase RIP3 phosphorylation in normal or oxygen-glucose deprivation/reoxygenation (OGD/R) conditions (P < 0.05).
CIRI activated Drp1 and accelerated the p62-mediated formation of autophagosomes while inhibiting the transition of autophagosomes to autolysosomes via the RIP1/RIP3 pathway activation. Undegraded autophagosomes were secreted extracellularly in the form of exosomes, leading to inflammatory cascades that further damaged mitochondria, resulting in excessive ROS generation and the blockage of autophagosome degradation, triggering a vicious cycle.
The recycling of cathode materials for spent NCM has always been a major concern for the energy industry. However, among the current processing methods, the general leaching efficiency of Li is ...between 85% and 93%, with much room for improvement. The recovery of Ni, Co and Mn requires a high cost of secondary purification. In this study, to recycle the NCM cathode material, a route of sulphated reduction roasting - selective Li water leaching - efficiency acid leaching of Ni, Co, Mn - extraction separation - crystallisation was adopted. The results showed that after roasting (a temperature of 800 °C, a reaction time of 90 min, a carbon content of 26%, and a sulphuric acid addition of n
H2SO4
:n
Li
= 0.85), Li water leaching efficiency was 98.6%, followed by acid leaching of Ni, Co and Mn at around 99%. Mn, Co were extracted with Di-(2-ethylhexyl) phosphoric acid and 2-Ethylhexyl phosphonic acid mono-2-ethylhexyl ester respectively to obtain Ni, Co, Mn solutions, which eventually were crystallized for manganese sulphate, cobalt sulphate, lithium carbonate and nickel sulphate products, with high purity of 99.40%, 98.95%, 99.10%, and 99.95%. The results of this study improved the leaching efficiency of Li and were closely linked to the actual industrial preparation of Ni, Co and Mn sulphates, providing a feasible and promising basis for spent NCM cathode materials industrial recovery.
Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, ...negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy.
This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18–65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2–T3 vs T4), and recurrent nodal stage (N0 vs N1–N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506.
Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3–53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 34% of 68 patients) versus the standard fractionation group (39 57% of 68 patients; between-group difference –23% 95% CI –39 to –7; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% 95% CI 64·4 to 84·8 vs 55·0% 43·4 to 66·6; hazard ratio for death 0·54 95% CI 0·33 to 0·88; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five 7% nasal haemorrhage) than in the standard fractionation group (16 24%, including two 3% nasopharyngeal necrosis, 11 16% nasal haemorrhage, and three 4% temporal lobe necrosis).
Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients.
Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.
Abstract
Background
Hypertrophy of ligamentum flavum (HLF) is the mainly cause of lumbar spinal stenosis (LSS), but the precise mechanism of HLF formation has not been fully elucidated. Emerging ...evidence indicates that transcription factor 7 (TCF7) is the key downstream functional molecule of Wnt/β-catenin signaling, which participated in regulating multiple biological processes. However, the role and underlying mechanism of TCF7 in HLF is still unclear.
Methods
We used mRNAs sequencing analysis of human LF and subsequent confirmation with RT-qPCR, western blot and immunohistochemistry to identified the TCF7 in HLF tissues and cells. Then effect of TCF7 on HLF progression was investigated both in vitro and in vivo. Mechanically, chromatin immunoprecipitation, dual-luciferase reporter assays, and rescue experiments were used to validate the regulation of TCF7/SNAI2/miR-4306 feedback loop.
Results
Our results identified for first time that the TCF7 expression was obviously elevated in HLF tissues and cells compared with control, and also found that TCF7 expression had significant positive correlation with LF thickness and fibrosis score. Notably, TCF7 inhibition suppressed the hyper-proliferation and fibrosis phenotype of HLF cells in vitro and ameliorated progression of HLF in mice in vivo, whereas TCF7 overexpression promoted hyper-proliferation and fibrosis phenotype of HLF cells in vitro. Our data further revealed that TCF7 interacted with SNAI2 promoter to transactivated the SNAI2 expression, thereby promoting hyper-proliferation and fibrosis phenotype of HLF cells in vitro. Furthermore, miR-4036 negatively regulated by SNAI2 could negatively feedback regulate TCF7 expression by directly binding to TCF7 mRNA 3’-UTR, thus inhibiting the hyper-proliferation and fibrosis phenotype of HLF cells in vitro.
Conclusions
Our study demonstrated that TCF7 inhibition could suppress HLF formation by modulating TCF7/SNAI2/miR-4306 feedback loop, which might be considered as a novel potential therapeutic target for HLF.
The mainstream research of social factors and box office performance has concentrated on post-consumption opinion mining and sentiment analysis, which are difficult to operationalize to the benefits ...of the industry practitioners whose objective is to maximize box office sales. In this study, we propose the Facebook “like” as an effective social marketing tool before the release of movies for several reasons. Firstly, people's prerelease “liking” of movies can be influenced by marketing campaigns. Secondly, the clicks of “likes” create social impact, as suggested by the Social Impact Theory, on moviegoers' consumption behaviors. And thirdly, Facebook “like” provides practitioners with real-time visible updates. By studying the impact of prerelease “likes” on box office sales, we not only contribute to the literature by offering a new social metric to evaluate the box office performance, but also provide the industry practitioners with quantitative support for the effectiveness of their social marketing activities. Our empirical results indicate that the prerelease “likes” exert a significantly positive impact on box office performance. More specifically, 1% increase in the number of “likes” in the one week prior to release is associated with an increase of the opening week box office by about 0.2%. As it approaches the release date, the prerelease “like” impact becomes stronger, suggesting that the latest prerelease “likes” are more effective in driving box office performance.
•We propose prerelease “like” as a social metric of box office performance.•We use Social Impact Theory to study the social impact of prerelease “likes”.•Prerelease “likes” exert a significantly positive impact on box office performance.•The prerelease “like” impact is stronger as it approaches release date.
Abstract
Coconut shell biochar and bamboo biochar were added to the bedding courses of permeable pavements to improve nitrogen removal efficiency. This was expected to be particularly effective for ...innovative permeable pavements that increase evaporation of stored rainwater. The effects of the rainfall intensity and ambient temperature on nitrogen removal were assessed. The NO3−-N removal rate for the pavements with biochar added and the blank controls were 48.6%–54.0% and 10.8%, respectively, at a rainfall intensity of 10 mm/h and temperatures of 22–28 °C. The total nitrogen removal rates for the pavements with biochar added and the blank controls were 52.6%–57.7% and 20%, respectively. Adding coconut shell and bamboo biochar improved denitrification without causing organic matter to be leached. Increasing the rainfall intensity and decreasing the temperature caused less nitrogen to be removed. The total nitrogen balance indicated that the innovative pavements and conventional pavements with the same biochar amendments removed 781.58 and 733.30 mg of nitrogen, respectively, suggesting that adding biochar improved the performances of the innovative pavements more than the conventional pavements. Quantitative polymerase chain reaction assays of bedding course samples indicated that adding biochar markedly increased the abundances of denitrifying microorganisms.
Xylem hydraulic characteristics govern plant water transport, affecting both drought resistance and photosynthetic gas exchange. Therefore, they play critical roles in determining the adaptation of ...different species to environments with various water regimes. Here, we tested the hypothesis that variation in xylem traits associated with a trade‐off between hydraulic efficiency and safety against drought‐induced embolism contributes to niche differentiation of tree species along a sharp water availability gradient on the slope of a unique river valley located in a semi‐humid area. We found that tree species showed clear niche differentiation with decreasing water availability from the bottom towards the top of the valley. Tree species occupying different positions, in terms of vertical distribution distance from the bottom of the valley, showed a strong trade‐off between xylem water transport efficiency and safety, as evidenced by variations in xylem structural traits at both the tissue and pit levels. This optimized their xylem hydraulics in their respective water regimes. Thus, the trade‐off between hydraulic efficiency and safety contributes to clear niche differentiation and, thereby, to the coexistence of tree species in the valley with heterogeneous water availability.
Quartz is an important component of shale and has a significant influence on shale physical properties. However, the specific effects that different quartz types exert on shale porosity evolution and ...brittleness remain unclear. A series of experiments including petrographic observations, geochemical analyses, and triaxial compress experiments were conducted on shale samples from the Wufeng-Longmaxi Formations in southern China. The Wufeng-Longmaxi samples have been classified into siliceous shale, argillaceous shale, and mixed shale. Several quartz types were identified in the shale samples, including extrabasinal detrital quartz and authigenic quartz (microcrystalline quartz, quartz overgrowths, and bioclastic quartz). Based on the different origins, the authigenic quartz was divided into biogenic quartz derived from the dissolution of siliceous organisms and S–I quartz derived from the conversion of smectite to illite. Bioclastic quartz, most microcrystalline quartz, and most quartz overgrowths are biogenic quartz. A small number of quartz overgrowths and microcrystalline quartz are S–I quartz. The quartz content of different genesis processes was quantitatively calculated using major and trace elements data collected via XRF. Quartz types in siliceous shale samples are dominated by biogenic quartz (avg. 49%). Extrabasinal detrital quartz is the primary quartz type in argillaceous shale samples (avg. 68%) and mixed shale samples (avg. 50%). Porosity reduction mechanisms in most of the Wufeng-Longmaxi shale samples are primarily compaction-dominated. Biogenic quartz acts as a pore protector rather than destroyer, while S–I quartz derived from the conversion of smectite to illite acts as a pore destroyer rather than protector. The brittleness index (BI) of siliceous shale samples is the highest of all the shale samples since the abundant biogenic microcrystalline quartz particles dispersed within the shale matrix connect rigid grains to form an interconnected force framework.
•The authigenic quartz in the Wufeng-Longmaxi shale samples was divided into biogenic quartz and S–I quartz.•Biogenic quartz acts as a pore protector rather than destroyer, but S–I quartz acts as a pore destroyer rather than protector.•Siliceous shale samples are featured by good brittleness, since the abundant microcrystalline quartz connect rigid grains to form a force framework.
To investigate the correlation between non-alcoholic fatty liver disease and visceral adipose tissue in non-obese Chinese adults using computed tomography (CT).
The study included 454 subjects ...undergoing abdominal CT scan. Degree of CT attenuation in liver and spleen, and the degree of fat infiltration in liver were evaluated according to three indices: the attenuation value of liver parenchyma (CT
), the attenuation ratio of liver and spleen (LS
) and the attenuation difference between liver and spleen (LS
). Visceral fat area (VFA) and total fat area (TFA) at L2/3 and L4/5 levels were measured, and the abdominal subcutaneous fat area (SFA) was calculated. Bivariate correlation analysis was carried out to determine the correlation among these factors.
In men, VFA, SFA and TFA at L2/3 and L4/5 levels showed significant differences in terms of the three indices to distinguish fatty liver from non-fatty liver (all,
< 0.001). In men, all the three indices showed negative correlation with TFA, SFA and VFA (all,
< 0.001). The negative correlation between the three indices and VFA at the L2/3 level was higher than at L4/5 level (
= -0.476 vs.
= -0.340 for CT
,
= -0.502 vs.
= -0.413 for LS
,
= -0.543 vs.
= -0.422 for LS
,
< 0.001, respectively). The negative correlation between LS
, LS
and VFA at L2/3 and L4/5 levels was higher than SFA at the corresponding level. In women, all the three indices showed negative correlation with VFA and TFA at L2/3 and L4/5 levels, and the negative correlation between CT
and VFA was higher at L2/3 level than at L4/5 level (
= -0.294 vs.
= -0.254,
< 0.001).
In non-obese Chinese adults, the degree of hepatic fatty infiltration showed a strong correlation with abdominal fat on CT. VFA at L2/3 level was more closely related to fatty liver compared with VFA at L4/5 level.
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