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The influence of withdrawal rate (3, 4.5,6,9 and 12 mm/ min) on microstructure and high temperature rupture properties of A3 alloy was investigated by testing the microstructure and properties of the third generation nickel-based single crystal superalloy. The results show that with the increase of withdrawal rate, the dendrite spacing decreased exponentially, the segregation degree of main elements and the content of (γ + γ) eutectic structure decreased, and the size of γ phase decreased. After heat treatment, the eutectic structure was dissolved basically, and the segregation of the forming elements of γ phase is eliminated at different withdrawal rates. The size of γ phase in dendrite is smallest of 372.3μm at 4.5 mm/ min, the pore content is significantly larger than that of as-cast alloy, and decreased firstly and then increased with the increasing of withdrawal rate, which is 0.112% at 4.5 mm/ min and 0.182% at 3 mm/ min. The rupture life of the alloy at 1100 °C/140MPa is the longest at 4.5 mm/ min, which is mainly determined by the precipitation of TCP phase, pore content and γ size.

A silicon waveguide with reverse-biased p-i-n junction is used to experimentally demonstrate all-optical regeneration of non-return-to-zero (NRZ) on-off keying (OOK) signal based on four-wave mixing. The silicon waveguide allows a high conversion efficiency of -12 dB. The 0.22 dB (1.1 dB) quality (Q) factor and 0.74 dB (6.3 dB) extinction ratio (ER) improvements on average are achieved for 100 Gb/s (50 Gb/s) NRZ OOK signal regeneration at different receiving powers via the optimal match between the input signal optical power and input-output transfer curve. To the best of our knowledge, this silicon-based all-optical regenerator exhibits superior regeneration performance, including large ER and Q factor improvements, and the highest regeneration speed of NRZ OOK signal, and it has wide applications in 5 G/6 G networks.

We acknowledge support from the University of St Andrews, the China Scholarship Council (studentship to YYG) and Leverhulme Trust (RPG-2018-065). Four new hybrid lead(II) halide perovskites, γ-(FA)2PbBr4, (FA)1.5(AA)0.5PbBr4, (PY)(GA)PbBr4 and (PY)(TZ)PbBr4 ((FA)=formamidinium, (AA)=acetamidinium, (PY)=pyrazolium, (GA)=guanidinium and (TZ)=1,2,3-triazolium), adopt (110)-oriented layered perovskite structures. While (PY) is found to template the formation of ‘conventional’ (110)-oriented structure types (i. e. containing staggered [PbBr4]∞ layers), (FA) is shown to facilitate formation of much less common variants based 3 : 1 ordering of the interlayer species or 3×2 step-like corrugation of the perovskite-like layers themselves. Postprint

Background Although an association between the cytochrome P4502D6 (CYP2D6) *10 (100C>T) polymorphism and hepatocellular carcinoma (HCC) is known, the mechanism remains unclear. Here we aimed to explore mechanisms of CYP2D6*10 (100C>T) polymorphism conferring to HCC, and screen markers for HCC. Methods Label-free global proteome profiling with 34 normal livers and peritumor tissue from 61 HCC patients was performed, and angiopoietin-like protein-6 (ANGPTL6) was evaluated in 2 liver samples validation cohorts and 2 blood specimens validation cohorts. Results We found a significantly decreased frequency of TT in HCC patients which reduced HCC susceptibility by 69.2% and was accompanied by lowered enzymatic activity for CYP2D6. Proteomic analysis revealed 1342 differentially expressed proteins (DEPs) that were associated with HCC and 88 DEPs were identified as 100 TT-related proteins, likely underlying the susceptibility to HCC. Twenty-two upregulated DEPs and 66 downregulated DEPs were mainly related to lipid metabolism and the extracellular matrix, respectively. High ANGPTL6 was associated with a higher risk to HCC and worse prognosis. ANGPTL6 was both an independent risk factor and an independent prognostic factor for HCC and exhibited strong potential for predicting HCC occurrence, with comparable AUC values and higher sensitivity compared with alpha-fetoprotein. Conclusions The TT genotype-associated decreased risk of HCC appears to be related to lowered CYP2D6 activity and altered protein expression in the tumor microenvironment, and ANGPTL6 is a promising new diagnostic and prognostic biomarker for HCC. Our findings reveal new mechanistic insights for polymorphisms related to HCC risk and provide avenues for screening for HCC.

Background Aortic pseudoaneurysm is a life-threatening clinical condition, and thoracic endovascular aortic repair (TEVAR) has been reported to have a relatively satisfactory effect in aortic pathologies. We summarized our single-centre experience using chimney TEVAR for aortic arch pseudoaneurysms with inadequate landing zones. Methods A retrospective study was conducted from October 2015 to August 2020, 32 patients with aortic arch pseudoaneurysms underwent chimney TEVAR to exclude an aortic lesion and reconstruct the supra-aortic branches, including 3 innominate artery, 12 left common carotid arteries and 29 left subclavian arteries. Follow-up computed tomography was suggested before discharge; at 3, 6, 12 months and yearly thereafter. Results The median age of 32 patients was 68.0 years (range, 28–81) with the mean max diameter of aneurysm of 47.9 ± 12.0 mm. Forty-four related supra-aortic branches were well preserved, and the technical success rate was 100%. The Type Ia endoleaks occurred in 3 (9%) patients. Two patients were lost to follow-up and 4 patients died during the follow-up period. The mean follow-up times was 46.5 ± 14.3 months. One patient died due to acute myocardial infarction just 10 days after chimney TEVAR and the other 3 patients passed away at 1.5 months, 20 months, and 31 months with non-aortic reasons. The 4.5-year survival estimate was 84.4%. The primary patency rate of the target supra-arch branch vessels was 97.7% (43/44), and no other aorta-related reinterventions and severe complications occurred. Conclusion For aortic arch pseudoaneurysms with inadequate landing zones for TEVAR, the chimney technique seems to be feasible, with acceptable mid-term outcomes, and it could serve as an alternative minimally invasive approach to extend the landing zone. Slow flow type Ia endoleak could be treated conservatively after chimney TEVAR. Additional experience is needed, and the long-term durability of chimney TEVAR requires further follow-up.

Background Exploring drugs that reverse drug resistance and increase the sensitivity of chemotherapy drugs could significantly improve treatment effect of cancer. Our study explored the reversal effect and possible molecular mechanisms of emodin on cisplatin resistance in A549/DDP cells. Methods The IC50 and resistance index of cells were determined by Cell Counting Kit-8 assay. The ability of cell proliferation was evaluated by wound healing assay. Transwell assay was used to detect cell invasion and migration. Apoptosis induction rate was determined by flow cytometry assay and 4',6- diamidino- 2-phenylindole staining. Intracellular concentration was determined by HPLC. Western blot analysis was applied to determine expressions of nuclear factor kappa beta (NF-κB) and its downstream proteins. Results In this study, we found that the growth inhibitory effect of cisplatin was significantly enhanced by emodin in A549/DDP cells. The combined use of emodin with DDP can effectively promote lung cancer cells apoptosis and inhibit cell migration and invasion. Further investigation indicated that reinforcement effect of emodin and DDP may be associated with inhibition of NF-κB pathway and drug efflux-related proteins such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and Glutathione S-transferase (GST). The key role of NF-κB was further confirmed by the application of NF-κB inhibitor Ammonium pyrrolidinedithiocarbamate. The intervention of both can significantly increase A549/DDP cell apoptosis and inhibit DDP-induced upregulation of P-gp, MRP and GST. Conclusions Emodin reverses the cisplatin resistance of tumor cells by down-regulating expression of P-gp, MRP and GST, increasing the intracellular accumulation in A549/DDP cells, and the effect may be associated with the NF-κB pathways.

The diamond-like carbon (DLC) film on 316L stainless steel substrate was prepared by pulsed plasma-enhanced chemical vapor deposition, and the performance of the films was optimized by regulating the pulse voltage. Microstructure and properties of DLC film on 316L stainless steel were characterized by atomic force microscopy, field-emission scanning electron microscopy, Raman spectra, nano-indenter and electrochemical workstations. The results showed that DLC films with smooth and dense morphology have a low friction coefficient and high nano-indentation hardness, and the surface hardness of 316L stainless steel substrate was enhanced by more than 3 times. The mechanical properties of DLC films and their bond with 316L stainless steel could be further optimized by increasing pulse voltage. DLC films on 316L stainless steel substrate increased the self-corrosion potential by 0.173 V and decreased self-corrosion current by 99%, which significantly improved the anti-corrosive properties of 316L substrate.

The melting mechanisms of Pt-based multimetallic nanoparticles (NPs) are important to help determine their optimal melting processes. To understand the melting and coalescence behaviors of heterogeneous NPs (Pd–Pt NPs) with various sizes and compositions, molecular dynamics (MD) simulation was employed. The MD results for larger Pd–Pt NPs with an effective diameter of 4.6–7.8 nm show that PtPd alloy can form at Pd/Pt interface before Pd NP melted completely, while for Pt-core/Pd-shell NP and Pd-core/Pt-shell NP, PtPd alloy formed only after Pd portion melted completely. For smaller Pd–Pt NPs with an effective diameter of 2.5–4.0 nm, PdPt alloy is not formed until both Pd and Pt NPs melted completely. Besides, the coalescence process of Pd–Pt NPs depends on the melting temperature of Pt NP when Pt composition is higher than 20 at%. Furthermore, the melting mechanisms of Pd/Pt/Ir trimetallic NPs are investigated. A two-step melting process occurs in Pd–Pt–Ir NPs and Ir-core/Pt-shell/Pd-shell NP, and the melting sequence of Pd-core/Pt-shell/Ir-shell NP and Pt-core/Pd-shell/Ir-shell NP is different from Pd/Pt bimetallic NPs. Graphical abstract: [Figure not available: see fulltext.]. Agency for Science, Technology and Research (A*STAR) Submitted/Accepted version The authors would like to acknowledge funding support from the Agency for Science, Technology and Research (A*STAR, No. SERC A1983c0032), AME Individual Research Grant (IRG), and the computing resources from National Supercomputing Centre Singapore.

All-optical regeneration of 100 Gb/s NRZ OOK signal with 3.6 dB extinction ratio and 0.5 dB quality factor improvements is experimentally demonstrated using a silicon waveguide with reverse-biased p-i-n junction for the first time. © 2022 The Author(s)

Unraveling the molecular mechanisms by which genetic variants of cytochrome P450 2A6 lead to different metabolic phenotypes remains a long-standing but important challenge. CYP2A6 is an enzyme involved in the metabolism of several clinical drugs as well as the metabolic activation of carcinogenic nitrosamines. Herein, CYP2A6 genotypes and phenotypes, as indicated by protein content [by liquid chromatography-mass spectrometry (MS)/MS] and metabolic activities [Vmax, clearance (CL)], were determined for 90 human liver samples. We determined the median, range, and interindividual and intraindividual variation of CYP2A6 content and activity at the microsomal, liver tissue, and whole liver level and predicted hepatic in vivo clearance by in vitro-in vivo extrapolation based on CYP2A6-mediated coumarin metabolism by each CYP2A6 genotype. These results reveal how different CYP2A6 genotypes yield different phenotypic traits in protein content and enzyme activity. For relative Vmax, CL, and protein content, the intraindividual percentage coefficients of variation (ICVs) were 41.0% (18.8%-125.1%), 28.5% (2.39%-133.5%), and 27.8% (2.68%-88.0%), respectively. The high ICVs implied large intraindividual variation at different levels, sometimes in a genotype-dependent manner. Intergenotype analysis revealed that the CYP2A6*4 allele demonstrated the most obvious effect on phenotypic outcomes, both in protein content and in metabolic activity. Indeed, decreased CYP2A6 protein content with the CYP2A6*4 genotype might explain the decreased metabolic activity from the molecular to the organismal level. These findings may allow useful predictions for CYP2A6-mediated drug metabolism on an individual patient basis in accord with the goal of achieving personalized medicine. SIGNIFICANCE STATEMENT: We provide the median, range, and interindividual and intraindividual variation in CYP2A6 content at the microsomal, liver tissue, and whole liver level by liquid chromatography-mass spectrometry (MS)/MS as well as activities at the protein, microsomal, liver tissue, and whole liver level both in vitro and at the organismal level based on CYP2A6-mediated coumarin metabolism with each CYP2A6 genotype, thereby allowing us to elucidate how different CYP2A6 genotypes yield differing phenotypic traits (protein content and enzyme activity), facilitating the development of personalized medicine.

In this paper, a 2D fluid model is built to reveal the inductively coupled Ar/O2 plasma behavior at 300 W, 30 mTorr, in the gas mixture of 95% Ar −5% O2 and 10% Ar −90% O2. The reliability of the model is first verified by comparing the calculated results with the experimental data, and the consistent results are obtained. Then, the spatial distributions of the charged species densities are investigated. As Ar fraction decreases, the maximum densities of charged particles shift toward the coil significantly, and the O2+ becomes the dominant positive ion at higher O2 fractions. The main reaction mechanisms are also discussed. It is concluded that the electrons are generated by the ionization of background gases, and the Ar+ ions are primarily formed by the ionization of Ar. However, the charge exchange processes account for the most production of O2+ and O+ ions at a high Ar fraction. The loss at the walls is the most important process to the consumption of positive ions. For the O− ions, they are first generated by the dissociative attachment of O2 at ground state, followed by the metastable state, and they are destroyed either by the ion–ion recombination with Ar+ ions or the detachment with O atoms as the Ar proportion varies. Finally, the effect of the ion–ion recombination reaction rate coefficients is discussed. The results indicate that rate coefficients of the recombination reactions have a significant influence on the positive ion densities when the Ar fractions are high.

BACKGROUND: Ulcerative colitis, as a kind of inflammatory bowel disease (IBD) is characterized by abdominal pain. This study aimed to investigate the effect of icariin (ICA) on the intestinal microflora of colitis mice. METHODS: Fifteen female C57BL/6 mice were randomly divided into the Control group, dextran sodium sulfate (DSS)-induced colitis (DSS) group, and ICA treatment (DSS+ICA) group. The severity of inflammation in DSS-induced colitis mice was evaluated using disease activity scoring (considering weight-loss percentage, stool-shape change, and stool-bleeding scoring). Pathological changes of mice intestinal tract were evaluated using hematoxylin–eosin (HE) staining. Serum levels of TNF-α and IL-6 were detected with enzyme-linked immunosorbent assay. Expressions of p65 and p-p65 (p-p65/p65 ratio) were analyzed using Western blot assay. 16S rDNA sequencing was used to analyze the abundance and composition of intestinal microflora. RESULTS: Compared with DSS group, ICA significantly improved disease activity (P < .05) and reduced inflammatory damage of colon tissues (P < .05) in DSS-induced colitis mice. Compared with the DSS group, mice in the ICA group demonstrated significant weight and colon length (P < .05). ICA significantly inhibited expressions of IL-6 and TNF-α compared to the DSS group (P < .05). p-p65/p65 ratio in the DSS+ICA group was remarkably enhanced compared to the DSS group (P < .05). ICA significantly reduced the proportion and activity of Bacteroides, Helicobacteraceae, Turicibacter, and significantly increased that of beneficial microflora (Lactobacillus, Lachnospiraceae, Akkermansia), so as improved damages of colon tissues. CONCLUSION: ICA can improve intestinal flora abundance and composition of DSS-induced colitis mice, and inhibit tissue damage and inflammatory response through modulating the p-p65/p65 expression. Keywords: Icariin, ulcerative colitis, intestinal microflora, dextran sulfate sodium, inflammation

The selectivity of gas sensing materials is increasingly important for their applications. The oxygen-regulated SnO2 films with (110) and (101) preferred orientation were obtained through magnetron sputtering, followed by annealing treatment. Their micro-structure, surface morphology and gas response were investigated by advanced structural characterization and property measurement. The results showed that the as-prepared (110)-oriented SnO2 film was oxygen-rich and had more adsorption sites while the as-prepared (101)-oriented SnO2 film was oxygen-poor and more sensitive to de-oxidation. H2 gas sensitivity, response speed, selectivity between H2 and CO of the (110)-orientated SnO2 film was superior to that of the (101)-orientated SnO2 film. After treated at high temperature and high vacuum, the reduction of gas-sensing properties of the annealed (110) SnO2 film was much more than that of the annealed (101) SnO2 film. The lattice oxygen was responsible for the difference in gas-sensing response between (110) and (101)-oriented SnO2 films under oxygen regulation. This work indicated the gas-sensing selectivity of the different crystal planes in SnO2 film, providing a significant reference for design and extension of the related materials.

Background To probe the differences of gut microbiota among major depressive disorder (MDD), bipolar disorder with current major depressive episode (BPD) and health participants. Methods Thirty one MDD patients, thirty BPD patients, and thirty healthy controls (HCs) were recruited. All the faecal samples were analyzed by shotgun metagenomics sequencing. Except for routine analyses of alpha diversity, we specially designed a new indicator, the Gm coefficient, to evaluate the inequality of relative abundances of microbiota for each participant. Results The Gm coefficients are significant decreased in both MDD and BPD groups. The relative abundances of increased phyla Firmicutes and Actinobacteria and decreased Bacteroidetes were significantly in the MDD and BPD groups. At genus level, four of top five enriched genera (Bacteroides, Clostridium, Bifidobacterium, Oscillibacter and Streptococcus) were found increased significantly in the MDD and BPD groups compared with HCs. The genera Escherichia and Klebsiella showed significant changes in abundances only between the BPD and HC groups. At the species level, compared with BPD patients, MDD patients had a higher abundance of Prevotellaceae including Prevotella denticola F0289, Prevotella intermedia 17, Prevotella ruminicola, and Prevotella intermedia. Furthermore, the abundance of Fusobacteriaceae, Escherichia blattae DSM 4481 and Klebsiella oxytoca were significantly increased, whereas the Bifidobacterium longum subsp. infantis ATCC 15697 = JCM 1222 was significantly reduced in BPD group compared with MDD group. Conclusions Our study suggested that gut microbiota may be involved in the pathogenesis of both MDD and BPD patients, and the nuances of bacteria may have the potentiality of being the biomarkers of MDD and BPD.

In this work, two types of transition layers (pure Cr and gradient CrNx) were fabricated between plasma-assisted nitrided (PAN) stainless steel and magnetron sputtering CrN coating to investigate the effect of transition layer on mechanical properties of CrN coating on PAN stainless steel substrates. For comparison, samples without transition layer were also synthesized. The phase structure, morphology, abrasive resistance and adhesion of the CrN coatings, as well as the nano-hardness and Young's modulus were investigated by XRD, SEM, ball-on-disk tribometer, scratch tester and nano-indentation tester, respectively. The results showed the transition layers of pure Cr and gradient CrNx absorbed the excess nitrogen diffusing outwards from the nitrided layer, and thus suppressed partly the precipitation. As a result, the adhesion force was improved to 22.5 and 25.7 N, respectively. The nano-hardness and Young's modulus of modified layers were improved to the range of 22.8–25.8 GPa and 331–347.3 GPa, corresponding to the substrate of 7.2 GPa and 230.5 GPa. The modified layer with no transition layer had the best wear resistance for nitriding of 1 h; while the layer with gradient CrNx had the best wear resistance for nitriding of 4 h.

The high-temperature phase behaviour of the ferroelectric layered perovskite Bi4Ti3O12 has been re-examined by high-resolution powder neutron diffraction. Previous studies, both experimental and theoretical, had suggested conflicting structural models and phase transition sequences, exacerbated by the complex interplay of several competing structural instabilities. This study confirms that Bi4Ti3O12 undergoes two separate structural transitions from the aristotype tetragonal phase (space group I4/mmm) to the ambient-temperature ferroelectric phase (confirmed as monoclinic, B1a1). An unusual, and previously unconsidered, intermediate paraelectric phase is suggested to exist above T C with tetragonal symmetry, space group P4/mbm. This phase is peculiar in displaying a unique type of octahedral tilting, in which the triple perovskite blocks of the layered structure alternate between tilted and untilted. This is rationalized in terms of the bonding requirements of the Bi3+ cations within the perovskite blocks.

The CrN coatings were performed on 316 L austenitic stainless steel, skh51 high speed steel, and YG8 cemented carbide using plasma-enhanced magnetron sputtering system. The adhesion and failure mechanism of the hard CrN coatings on different kinds of substrates were investigated. The morphology, microstructure, crystallinity, as well as nano-hardness and Young' modulus of the as-deposited coatings were investigated by scanning electron microscopy, X-ray diffraction, and nano-indentation testing system, respectively. In particularly, the adhesion and failure mechanism of different coating-substrate systems were evaluated by scratch and indentation tests. Apparently, the adhesion and failure mechanism of the CrN coatings were significantly influenced by the species of substrates. The results of the scratch test indicated that the increase of adhesion strength (Lc = 190 N) of the CrN coating to YG8 was associated with the formation of the obvious indented coating-substrate interface, and the higher modulus of the substrate, which provided a better load-carrying capacity, whereas the CrN coating deposited on 316 L in contrast. In Rockwell indentation test, the main failure mechanism of the CrN coatings on substrate with high modulus were mainly brittle fracture, whereas the CrN coatings deposited on soft substrate was failed in ring cracks, which was attributed to the asynchronous recovery between the substrate and the coating.

We acknowledge support from the University of St Andrews, the China Scholarship Council (studentship to YYG) and the Leverhulme trust (RPG-2018-065). The hybrid perovskites (ImH)(GuH)PbBr4 and (TzH)(GuH)PbBr4 (ImH+ = imidazolium, GuH+ = guanidinium, TzH+ = 1,2,4-triazolium) both adopt (110)-oriented layer structures. However, the GuH+ cation adopts differing crystallographic sites in the two structures (intra-layer versus inter-layer); this is discussed in terms of the sizes of the organic cations and their hydrogen-bonding preferences. Postprint

We acknowledge support from the University of St Andrews, the China Scholarship Council (studentship to YYG) and Leverhulme Trust (RPG-2018-065). A new hybrid lead(II) halide perovskite, (TzH)2PbCl4, ([TzH+] = 1,2,4-triazolium), adopts a (001)-oriented layered perovskite structure, which can be considered as derived from the n = 1 Ruddlesden-Popper (RP) type. Variable temperature single crystal X-ray diffraction reveals a structural phase transition in the region 125 K < T < 173 K between a high temperature, high symmetry polymorph, space group Cmcm, and a low temperature, low symmetry chiral polymorph, space group P212121, which has a tripled unit cell volume. UV-Vis spectra suggest a band gap of 3.30 eV for (TzH)2PbCl4. A second polymorph of the bromide analogue, (TzH)2PbBr4-Ⅱ, is also reported, and structural relationships between all three variants are discussed. Postprint

The effective inhibition of nitrite oxidizing bacteria (NOB) is the key to realizing satisfactory nitrite accumulation and achieving effective nitritation. In order to explore the selective effect of hydroxylamine (NH

Three new 1D chain structure type hybrid organic-inorganic lead(ii) halides are presented: IQPbBr3, QPbBr3 and QPbI3, templated by large organic cations, isoquinolinium ([IQ+] = protonated isoquinoline) and its isomer quinolonium ([Q+] = protonated quinoline). All three compounds possess the same generic formula as cubic perovskite, ABX3, but adopt different structures. IQPbBr3 adopts a 1D face-sharing single chain hexagonal perovskite structure type, and the other two, QPbBr3 and QPbI3, adopt a non-perovskite structure which is built from 1D edge-sharing octahedral double chains. Crystal structures and preliminary photophysical properties are discussed. Two of them have lower bandgaps than the other reported materials with the same structure type, indicating the value of further exploratory studies for these types of materials.

Y.-Y.G. and T.L. acknowledge the University of St Andrews and China Scholarship Council for funding of studentships (201603780005) and (201606280032), respectively. J.A.M. and P.L. acknowledge financial support from the Leverhulme trust (RPG-2018-065). S.B., K.S. and F.P. acknowledge financial support from the German National Science Foundation via the Projects 423895689, KO 3973/2-1 and PA 3373/3-1 and further acknowledge support by the Bavarian State Ministry of Science, Research, and the Arts for the Collaborative Research Network ‘‘Solar Technologies go Hybrid’’. We present three new hybrid layered lead(II) bromide perovskites of generic composition A2PbBr4 or AA′PbBr4, which exhibit three distinct structure types. [TzH]2PbBr4, ([TzH+]= 1,2,4-triazolium), adopts a (001)-oriented layer structure, [AaH]2PbBr4, ([AaH+] =acetamidinium), adopts a (110)-oriented type, whereas [ImH][TzH]PbBr4, ([ImH+] =imidazolium),adopts a rare (110)-oriented structure with enhanced corrugation (i.e. ‘3 ×3’ type). The crystal structures of each are discussed in terms of the differing natureof the templating molecular species. Photoluminescent spectra for each are reported and the behaviours discussed in relation to the different structure of each composition. Postprint

Purpose:To evaluate the safety and feasibility of the in situ needle fenestration (ISNF) technique for reconstruction of the left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR) of complicated aortic arch pathologies.Materials and Methods:A retrospective review was conducted from January 2014 to December 2019 of 50 patients (mean age 60.2±11.1; 45 men) who underwent ISNF to revascularize the LSA during TEVAR. Twenty-one of the patients also required revascularization of the left common carotid artery (LCCA; n=19) and innominate artery (IA; n=2) using physician-modified in vitro fenestration. Overall, 73 supra-aortic branches were targeted for revascularization.Results:ISNF was successful in 48 patients (96%); one LSA could not be stented and a tortuous LSA prevented the needle from fenestrating the graft. No perioperative major adverse event occurred. There were no type I and 4 type III endoleaks (8%), 3 of which occurred among the first 20 cases. Types II and IV endoleaks were found in 3 (6%) and 6 (12%) cases, respectively; all disappeared during a median follow-up of 15 months (range 3–66). One death (2%) occurred within 12 months due to cerebral hemorrhage. Two patients (4%) required open reinterventions at 6 and 62 months.Conclusion:ISNF for revascularization of the LSA during TEVAR seems to be feasible with acceptable midterm outcomes. The learning curve and evolving patient selection criteria affected technical success, complications, and the need for reinterventions. Long-term durability requires further evaluation.

We present three new hybrid layered lead(II) bromide perovskites of generic composition A

According to traditional Chinese medicine,quot;spleen transportquot; is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aβ_(25-35) oligomers(final concentration 40 μmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aβ_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aβ-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 μmol·L~(-1) Aβ_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aβ_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aβ_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aβ_(25-35) transport across the blood-brain barrier.

BACKGROUND The metabolic processing of ellagic acid (EA) by cytochrome P450s (CYP450s) expressed in the intestines is unclear. This study aimed to investigate the effects of CYP450s that are highly expressed in HIEC cells on metabolic activity of EA. MATERIAL AND METHODS HIEC cell models expressing 2B6, 2C9, 2D6, and 3A4 were generated by stably transfecting with CYP450 genes using a lentivirus system. PCR and Western blot assay were used to detect expression of CYP450s. Cell Counting Kit-8 (CCK-8) assay was used to examine the cytotoxic effect of EA on CYP450s-expressing HIEC cells. Flow cytometry was employed to evaluate apoptosis of CYP450s-expressing HIEC cells after addition of EA. Metabolic clearance rate of EA in vitro by the constructed HIEC cell models was measured using UPLC-MS method. RESULTS CYP450s expression HIEC cell models, including CYP2B6, CYP2C9, CYP2D6, and CYP3A4, were successfully established. EA treatment at different concentrations (10 μg/mL and 50 μg/mL) remarkably decreased cell viability of HIEC cells expressing CYP2C9 compared to the untreated control (p

UDP-glucuronosyltransferase 2B7 (UGT2B7) is one of the most significant isoforms of UGTs in human liver. This research measured UGT2B7 protein content and activities, including maximum velocity (Vmax) and intrinsic clearance (CLint), in human liver at isoform, microsomal, liver tissue, and liver levels and identified the factors that influence expression. We determined absolute protein content by liquid chromatography-tandem mass spectroscopy and activities using the probe drug zidovudine in 82 normal human liver microsomes. Using a bottom-up method for derivation, we showed UGT2B7 content at the microsomal, liver tissue, and liver levels, as well as activities at the isoform, microsomal, liver tissue, and liver levels in vitro, and predicted hepatic clearance in vivo, with median, range, variation, and 95% and 50% prediction intervals. With regard to the intrinsic activities, the maximum velocity (Vmax) had a median (range) of 7.5 (2-24) pmol/min per picomole of 2B7, and the CLint was 0.08 (0.02-0.31) μl/min per picomole of 2B7. Determinations at liver level showed larger variations than at microsomal level, so it was more suitable for evaluating individual differences. By analyzing factors that affect UGT2B7, we found that: 1) The content at the liver tissue and liver levels correlated positively with activities; 2) the mutant heterozygotes of -327G>A, -900A>G, -161C>T may lead to decreased protein content and increased intrinsic CLint; and 3) the transcription factor pregnane X receptor mRNA expression level was positively associated with the measured protein content. In all, we showed that protein content and activities at different levels and the factors that influence content provide valuable information for UGT2B7 research and clinically individualized medication.

Hepatocellular carcinoma (HCC) is highly chemoresistant and therefore challenges both physicians and patients. Augmenter of liver regeneration (ALR), previously also known as 'hepatic stimulator substance', is reported to inhibit the epithelial-mesenchymal transition (EMT) in HCC, one of the frequent events that occur in cancer metastasis, suggesting that ALR is involved in HCC. In this study, we report for the first time that the transfection of ALR enhances the antitumor effect of chemotherapy with doxorubicin, a typical anticancer drug, on HCC in vitro and in vivo. The efflux of doxorubicin from ALR-transfected HCC cells is efficiently suppressed. This implies the intracellular retention of doxorubicin in tumor cells, which is at least partly attributable to the effective inhibition of ABCB1 and ABCG2 transporter expression in ALR-expressing cells. The downregulation of ALR expression by short hairpin RNA diminishes the antitumor effect of ALR. We further demonstrate that ALR inhibits the AKT/Snail signaling pathway, resulting in the downregulation of ABCB1 and ABCG2 expression. In conclusion, our results suggest that ALR is a potential chemotherapeutic agent against HCC.