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Background: Sex disparities in acute large vessel occlusion (LVO) following endovascular treatment (EVT) have been recently reported. However, there is uncertainty about the effect of sex differences on functional outcomes after EVT, particularly in an Asian population. The present study aimed to compare the clinical and safety outcomes between men and women with anterior circulation LVO treated with EVT. Methods: We analyzed data from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke: a Prospective Multicenter Registry Study) Registry, which was conducted at 111 hospitals from 26 provinces in China between November 2017 and March 2019. Men and women with anterior circulation LVO treated with EVT were matched using propensity scores. After a 1:1 propensity score matching, we compared the clinical outcomes including 90-day ordinal modified Rankin Scale distribution (primary outcome), procedure duration, successful reperfusion, symptomatic intracranial hemorrhage, and mortality. Furthermore, we explored sex modification on the primary outcome in subgroup analysis. Results: Of 1321 patients, 483 (36.6%) were women and 838 (63.4%) were men. The mean age for women and men were 68 and 62 years old, respectively. Among 578 patients identified after matching, there were no sex differences (men versus women) in 90-day ordinal modified Rankin Scale distribution (median [interquartile range], 4 [1–5] versus 3 [1–5], P =0.464), successful reperfusion (86.5% versus 91.0%, P =0.089), symptomatic intracranial hemorrhage (6.5% versus 7.9%, P =0.512), and mortality within 90 days (17.7% versus 17.0%, P =0.826). However, men had a longer median procedure duration than women (86 [52–128] versus 72 [48–110] minutes, β=14.51, [95% CI, 4.19–24.84]; P =0.006). Subgroup analysis showed that in patients with National Institutes of Health Stroke Scale score P for interaction=0.032). Conclusions: Overall, this matched-control study from the ANGEL-ACT study showed similar clinical outcomes between men and women with anterior circulation LVO treated with EVT. However, in the subgroup of patients presenting with lower stroke severity (ie, National Institutes of Health Stroke Scale score Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.

Background The prognosis of lung cancer varies widely, even in cases wherein the tumor stage, genetic mutation, and treatment regimens are the same. Thus, an effective means for risk stratification of patients with lung cancer is needed. Purpose To develop and validate a combined model for predicting progression-free survival and risk stratification in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treated with ensartinib. Material and Methods We analyzed 203 tumor lesions in 114 patients and evaluated average radiomic feature measures from all lesions at baseline and changes in these features after early treatment (Δradiomic features). Combined models were developed by integrating clinical with radiomic features. The prediction performance and clinical value of the proposed models were evaluated using receiver operating characteristic analysis, calibration curve, decision curve analysis (DCA), and Kaplan–Meier survival analysis. Results Both the baseline and delta combined models achieved predictive efficacy with a high area under the curve. The calibration curve and DCA indicated the high accuracy and clinical usefulness of the combined models for tumor progression prediction. In the Kaplan–Meier analysis, the delta and baseline combined models, Δradiomic signature, and two selected clinical features could distinguish patients with a higher progression risk within 42 weeks. The delta combined model had the best performance. Conclusion The combination of clinical and radiomic features provided a prognostic value for survival and progression in patients with NSCLC receiving ensartinib. Radiomic-signature changes after early treatment could be more valuable than those at baseline alone.

A set of ionic liquid capped polyimide membranes was prepared using 1-aminoethyl-3-methylimidazolium hexafluorophosphate (IL1) and 1-aminopropylimidazolium bis(trifluoromethylsulfonyl)imine (IL2) as the terminal groups. The products’ molecular weights, mechanical properties, and separation permeability (CO2/CH4) were investigated. For CO2/CH4 separation, the selectivity of the ionic liquid capped polyimide membranes was higher than that of noncapped ones. Among them, the membrane synthesized by 4.4′- diaminodiphenyl ether and 4.4′-(hexafluoroisopropyl) diphthalic anhydride (6FDA) as monomer, with IL1 as terminal group, displayed the best selectivity. Its permeability was 7.47 Barrer and selectivity 102.42, which exceeded the 1991 Robeson curve. Polyimide membranes capped by ionic liquid showed high gas selectivity and good gas permeability as well as good physical and chemical properties. Consequently, it can be concluded that introducing an ionic liquid structure to polyimide chains could make attractive membrane materials for various gas separation and related applications.

Background: The role of stroke etiology subtype in patients with acute large vessel occlusion on the occurrence of hemorrhagic transformation (HT) after endovascular treatment is poorly studied, and which factors mediate their relationship remains largely unknown. We utilized nationwide registry data to explore the association of stroke subtype (cardioembolism versus large artery atherosclerosis) with HT and to identify the possible mediators. Methods: A total of 1015 subjects were selected from the ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke)—a prospective consecutive cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals in China between November 2017 and March 2019—and divided into large artery atherosclerosis (n=538) and cardioembolism (n=477) according to the Trial of ORG 10172 in Acute Stroke Treatment criteria. The types of HT included any intracerebral hemorrhage (ICH), parenchymal hematoma, and symptomatic ICH within 24 hours after endovascular treatment. The association between stroke subtype and HT was analyzed using a logistic regression model. Mediation analysis was done to assess how much of the effect of stroke subtype on HT was mediated through the identified mediators. Results: Stroke subtype (cardioembolism versus large artery atherosclerosis) was associated with increased risk of any ICH (29.8% versus 16.5%; odds ratio, 2.03 [95% CI, 1.22–3.36]), parenchymal hematoma (14.3% versus 5.4%; odds ratio, 2.90 [95% CI, 1.38–6.13]), and symptomatic ICH (9.9% versus 4.7%; odds ratio, 2.59 [95% CI, 1.09–6.16]) after adjustment for potential confounders. The more thrombectomy passes in cardioembolism patients had a significant mediation effect on the association of stroke subtype with increased risk of HT (any ICH, 15.9%; parenchymal hematoma, 13.4%; symptomatic ICH, 14.2%, respectively). Conclusions: Stroke subtype is an independent risk factor for HT within 24 hours following endovascular treatment among acute large vessel occlusion patients. Mediation analyses propose that stroke subtype contributes to HT partly through thrombectomy pass, suggesting a possible pathomechanistic link. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.

The model plantPhyscomitrium patens(P. patens) has played a pivotal role in enhancing our comprehension of plant evolution, growth, and development. However, the current genome harbors numerous intricate regions that remain unfinished and erroneous. To address these issues, we present an exemplary assembly of theP. patensnuclear genome, which incorporates telomeres and centromere regions, thereby establishing it as the telomere-to-telomere (T2T) genome in a non-seed plant. This T2T genome not only dispels the prevailing misconception regarding chromosome number inP. patensbut also provides indispensable resources for conducting in-depth studies in moss genomics and biology.

SummaryGenomic rearrangements contribute to gene copy number alterations, disruption of protein-coding sequences and/or perturbation of cis-regulatory networks. SCRaMbLE, a Cre/loxP-based system implanted in synthetic yeast chromosomes, can effectively introduce genomic rearrangements, and is thus a potential tool to study genomic rearrangements. However, the potential of SCRaMbLE to study genomic rearrangements is currently hindered, because a strain containing all 16 synthetic chromosomes is not yet available. Here, we constructed a yeast strain, SparLox83, containing 83 loxPsym sites distributed across all 16 chromosomes, with at least two sites per chromosome. Inducing Cre recombinase expression in SparLox83 produced versatile genome-wide genomic rearrangements, including inter-chromosomal events. Moreover, SCRaMbLE of the hetero-diploid strains derived from crossing SparLox83 with strains possessing synthetic chromosome III (synIII) from the Sc2.0 project led to increased diversity of genomic rearrangements and relatively faster evolution of traits compared to a strain with only synIII. Analysis of these evolved strains demonstrates that genomic rearrangements can perturb the transcriptome and 3D genome structure and can consequently impact phenotypes. In summary, a genome with sparsely distributed loxPsym sites can serve as a powerful tool to study the consequence of genomic rearrangements and help accelerate strain engineering in Saccharomyces cerevisiae.

Abnormal expression of miR-199 is related to proliferation of Parkinson’s cells. Lipid nano emulsions can effectively inhibit cell growth. This study mainly explored whether lipid nano emulsions may regulate the expression of miR-199, thereby affecting Parkinson’s cells. SH-SY5Y Parkinson’s cells treated with 20 μmol/L miR-199 in SH-SY5Y cells, or both 20 μmol/L lipid nanoemulsion were used to intervene SH-SY5Y cells. Intervention time was set at 0, 6, 12, and 24 h, respectively. We used 20 μmol/L lipid nano emulsion to interfere with SH-SY5Y cells that were transfected with miR-199. We observed proliferation number and cell cycle changes after lipid nanoemulsion intervention in the SH-SY5Y cells. We also observed the expression of NF-κB pathway factor protein and verified that P65 is the direct downstream of miR-199. The higher the concentration of lipid nanoemulsion was, the more significant the decreased cell proliferation. The concentration of lipid nanoemulsion was 20 μmol/L, which decreased obviously (P < 0.01). Cell numbers in 20 μmol/L curcumin lipid nanoemulsion began to show an evident downward trend from 24 h, where cells from the G0/G1 phase increased and those in G2/M phase decreased significantly (P < 0.05). The higher the dose of lipid nanoemulsion, the higher the miR-199 expression, which showed a concentration and dose-dependence. The number of cells in the lipid nanoemulsion+miR-NC group was lowest. NF-κB is the direct target gene of miR-199. When the lipid nanoemulsion concentration was 20 μmol/L, the expression of P65 protein decreased. Lipid nano emulsion can therefore inhibit proliferation of Parkinson’s cells, and cell number in the S phase and G2/M phase, so that many cells are blocked in the G0/G1 phase, which then control cell growth. Lipid nano emulsion works mainly through miR-199/NF-κB axis, where miR-199 negatively regulates the NF-κB pathway, and ultimately controls abnormal cell proliferation.

Radiation-induced segregation (RIS) is a typical non-equilibrium process that can dramatically alter the behavior of defect sinks and material properties under irradiation. However, RIS mechanisms have been rarely studied around small He bubbles owing to the technical challenges involved in direct measurements of local chemistry. Here, using state-of-the-art atom probe tomography, we report the RIS behavior near He bubbles in the FeNiCoCr high-entropy alloy that indicates Co segregates most strongly, followed by weaker Ni segregation, whereas Fe and Cr are depleted almost to the same degree. Exceptionally, the magnitude of Co segregation around He bubbles is higher than previously measured values at voids and dislocation loops. Electron energy-loss spectroscopy was used to measure the He density and pressure inside individual bubbles. We demonstrate that He bubbles are over-pressurized at the irradiation temperature that could result in the vacancy bias and the subsequent vacancy-dominated RIS mechanism. First-principles calculations further reveal that there are repulsive interactions between He and Co atoms that may reduce the frequency of Co-vacancy exchange. As a result, He atoms likely retard Co diffusion via the vacancy mechanism and enhance the heterogeneity of RIS in Co-containing multicomponent alloys. These insights could provide the basis for understanding He effects in nuclear materials and open an avenue for tailoring the local chemical order of medium-and high-entropy alloys.

A novel SERS biosensor to detect the development of SAH and its induced complications from cerebrospinal fluid is reported.

In the current work, a parallel comparison of the influence of Al, Mo and Ti, on the microstructure and strengthening of the CoCrFeNi alloy was conducted. To achieve this, inconsistencies on variables including the extent of alloying, thermomechanical processing and property-evaluation method were avoided. Microstructurally, following cold-rolling, annealing of the 4 at.% Al-doped alloys at 800–1000 °C did not result in phase separation; nevertheless, that of the 4 at.% Mo- and Ti-doped alloys led to the respective formation of σ and η phase and, consequently, caused extra strengthening through the Orowan dislocation bypassing mechanism. Our systematic qualitative analysis and DFT calculations showed that Al and Ti are more effective than Mo in reducing the stacking fault energy (SFE) of the CoCrFeNi alloy, because they can induce more considerable deformation of electronic density, making the gliding of atomic layers easier. Following identical thermomechnical processing, Al-, Mo-, and Ti-doping causes different extent of solid solution strengthening and grain boundary strengthening. Mo causes the most pronounced solid solution strengthening but does not benefit the grain boundary strengthening; in contrast, the effectiveness of grain boundary strengthening is boosted by the doping Al and Ti. Current analyses support that Labusch instead of Fleischer mechanism is applicable to explain the differences in solid solution strengthening, and the observed differences in grain boundary strengthening arise from the different tendency of Al, Mo and Ti to reduce the SFE of CoCrFeNi. In addition, we determined the value of the dimensionless parameter f in the Labusch model for CoCrFeNi-based alloys and observed a close relation between Hall-Petch slope and SFE. Although more in-depth studies are needed to provide full and mechanistic understandings, both these findings in fact presents significant values toward designing novel single-phase high-strength CoCrFeNi-based alloys through manipulating the solid solution and grain boundary strengthening by compositional tuning.

In chemical mechanical polishing (CMP) process, chemical action is generally determined by pH regulator and oxidant in the polishing slurry. In this paper, tungsten was polished by CMP, and the material removal mechanism was discussed. The influence of pH values and H2O2 concentrations on surface quality and material removal rate (MRR) were studied deeply. The oxidation and dissolution kinetics of tungsten/tungsten oxide (W/WOx) during CMP process were investigated by electrochemical analysis and XPS. In addition, the microstructure of tungsten surface and its elemental composition and electronic state were also analyzed by SEM, white light interference and other characterization methods. Results reveal that tungsten has the best passivation effect at acidic pH, and the surface roughness increases with the increase of pH value, while the addition of H2O2 will deteriorate the surface quality of tungsten and improve the MRR. Besides, the different morphologies (corrosion pits, grain boundaries, etc.) formed after W-CMP indicate that the material removal mechanism is related to the composition of slurry.

SUMMARYThe genome of an organism is inherited from its ancestor and keeps evolving over time, however, how much the current version could be altered remains unknown. Here, we use the left arm of chromosome XII (chrXIIL) as an example to probe the genome plasticity in Saccharomyces cerevisiae. A neochromosome was designed to harbor originally dispersed genes. The essentiality of sequences in chrXIIL was dissected by targeted DNA removal, chromosome truncation and random deletion. Notably, 12 genes were sufficient for survival, while 25 genes are required to retain robust fitness. Next, we demonstrated these genes could be reconstructed using synthetic regulatory sequences and recoded open-reading frames with “one-amino-acid-one-codon” strategy. Finally, we built a neochromsome, which could substitute for chrXIIL for cell viability, with these reconstructed genes. Our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional chromosomes with completely artificial sequences.HIGHLIGHTSA neochromosome was designed to facilitate the assembly of exogenous DNA for stable expression in yeastThe left arm of chrXII could be minimized to just 12 genes to maintain viability, but additional genes were required to retain robust fitnessComprehensive recoding and transcriptional refactoring using artificial regulatory sequences produced a functional chromosome armA completely reconstructed neochromosome could replace the chrXIIL to maintain comparable fitness

Donghui Hou,1 Weihua Li,2 Sicong Wang,3 Yao Huang,1 Jianwei Wang,1 Wei Tang,1 Lina Zhou,1 Linlin Qi,1 Ning Wu,1,4,&ast; Shijun Zhao1,&ast; 1Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3GE Healthcare, Life Sciences, Beijing, People’s Republic of China; 4PET-CT Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijun Zhao; Ning WuDepartment of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 10021, People’s Republic of ChinaTel +86-10-8778-8550; Tel/Fax +86-10-8778-7523Email zsj.2001@163.com; cjr.wuning@vip.163.comPurpose: Although patients with primary and acquired epidermal growth factor receptor (EGFR) T790M positive non-small-cell lung cancer (NSCLC) respond to osimertinib treatment, the optimal treatment strategy differs for these two groups of patients. This study aimed to compare the clinicopathologic and computed tomography (CT) imaging characteristics between primary and acquired EGFR T790M mutations in patients with NSCLC before treatment.Patients and Methods: We enrolled two groups of patients with primary or acquired EGFR T790M mutation NSCLC (n = 103 per group) from January 2012 to December 2019. We analyzed their clinicopathologic and CT characteristics and differences between the groups. The groups were further categorized based on 21L858R and 19del to exclude the effect of coexistent mutations.Results: Primary, compared to acquired, T790M mutation tends to coexist with 21L858R (P < 0.001), exhibiting earlier tumor stage (P < 0.001), higher differentiation (P = 0.029), higher proportion of lepidic subtype adenocarcinoma (P < 0.001), and significant associations with some CT features (multiple primary lung cancers, ground-glass opacity, air bronchogram, and vacuole sign [all P < 0.001]). The combined model, composed of clinicopathologic and conventional CT signature and CT-radiomic signature, showed good discriminative ability with the area under the receiver operating characteristic curve 0.90 and 0.91 in the training and validation datasets, respectively. The T790M mutation contributed to these differences independently of coexistent mutations.Conclusion: We identified clinicopathologic and CT imaging differences between primary and acquired T790M mutations. These findings provide insights into developing future personalized T790M mutation status-based theranostic strategies.Keywords: non-small-cell lung cancer, T790M mutation, osimertinib, clinicopathologic characteristic, computed tomography

High-entropy carbide ceramics (HECCs) exhibited a series of property superiority, such as high hardness, high oxidation resistance and adjustable range of thermal conductivity, making them great candidates for structural materials used in extreme service conditions. However, current HECC-related reports can only provide limited guidance for the design of HECC materials with promising properties and stable structure or for their high-quality fabrication. To fill this gap, we proposed in the current review that integrated efforts should be taken in the following three aspects to advance the design and fabrication of high-performance HECCs. First, the rule for the single-phase formation needs to be theoretically identified using high-throughput density functional theory calculations (HTDFT) and a highly accurate predictive model for rapid compositional design warrants establishment through the combination of HTDFT and machine-learning studies. In parallel with the compositional design, the lack of theoretical foundation and guidance for the synthesis of highly dense and highly pure HECC materials necessitates extensive studies focusing on the principle for the synthesis of HECC pre-alloy powders and on the powder densification mechanisms during high-temperature sintering. Moreover, great attentions are to be paid to the mechanistic understandings on the mechanical, oxidation and thermal conduction behaviors of HECC materials; for example, the toughening and strengthening mechanisms of HECC materials could be elucidated through discerning the “HECC composition-stacking fault energy distribution/bonding state-dislocation behavior” correlations.

Cellulose acetate (CA) grafted with imidazole ionic liquids (CA-ILs) was synthesized by reacting CA with imidazole ionic liquids ([HO2CMmim]Cl, [HO2CEtmim]Cl, and [HO2CMmim]Br) by using tetrahydrofuran (THF) as the solvent and pyridine as the catalyst. The CA and CA-IL films were fabricated by using the casting solution method. The CA-IL films exhibited good film forming ability and mechanical properties. The successful grafting of CA with imidazole ionic liquids was confirmed by Fourier transform infrared (FTIR), 1H NMR, scanning electron microscopy (SEM), and elemental analysis, and the grafting degrees were 2.24, 2.45, and 3.30%, respectively. The CO2 permeation properties of the CA-IL films were 65.5, 105.6, and 88.3 Barrer, increased up to 2.0, 3.2, and 2.7 times, respectively, as compared to pure CA (32.6 Barrer). The CO2/CH4 selectivities of the CA-IL films were 15.6, 12.6, and 19.2, increased up to 1.7, 1.4, and 2.1 times, respectively, as compared to pure CA (9.26). Therefore, it can be concluded that the imidazole ionic liquids are immensely useful for improving the gas separation performance of CA films.