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Abstract The lncRNA NEAT1 has been shown to promote the progression of several cancers, containing laryngeal squamous cell carcinoma (LSCC). However, the precise mechanism by which it promotes LSCC progression remains unclear. In this study, we verified the high expression of lncRNA NEAT1 in LSCC tissues and cells using RT-qPCR. Analysis of clinical data exhibited that high expression of lncRNA NEAT1 was associated with a history of smoking, worse T stage, lymph node metastasis, and later TNM stage in patients with LSCC. The promotion effect of lncRNA NEAT1 on LSCC cell proliferation, migration, invasion, and tumor growth in vivo was verified by CCK-8, plate clone formation, Transwell, and nude mouse tumorigenicity assays. Bioinformatics prediction and double luciferase reporter gene assay verified the binding of miR-411-3p to lncRNA NEAT1 and FZD3 mRNA, and inhibition of miR-411-3p reversed the inhibitory effect of lncRNA NEAT1 on FZD3 expression in LSCC cells. We also verified that lncRNA NEAT1-mediated FZD3 activation in the Wnt pathway affects LSCC development. In conclusion, we demonstrate that lncRNA NEAT1 promotes the progression of LSCC, and propose that the lncRNA NEAT1/miR-411-3p/FZD3 axis may be an effective target for LSCC therapy.

The strain-hardening geopolymer composite (SHGC) is a new type of fiber concrete with excellent ductility and environmental friendliness. However, the high cost of fibers greatly limits its widespread application. This paper proposes the use of untreated low-cost polyvinyl alcohol (PVA) fibers and polyethylene (PE) fibers to develop a low-cost, high-performance SHGC. Axial compression and axial tension tests were conducted on the SHGC with different PE fiber volume fractions (1%, 1.5%, and 2%) and different PVA fiber replacement ratios (0%, 25%, 50%, 75%, and 100%) to investigate the hybrid effects of fibers with different surface properties and to reveal the mechanism of fiber hybridization on the mechanical behavior of SHGCs. The results show that increasing the PE fiber volume fraction improves the compressive and tensile ductility of the SHGC while increasing the PVA fiber replacement rate impacts the strength indicators positively due to the good interface effect formed between its hydrophilic surface and the matrix. When the PVA fiber replacement ratio is 100%, the compressive strength (93.4 MPa) of the SHGC is the highest, with a 21.1% increase compared to the control group. However, the tensile strength shows a trend of first increasing and then decreasing with the increase in the PVA fiber replacement ratio, reaching the highest at a 25% replacement ratio, with a 12.5% increase compared to the control group. Furthermore, a comprehensive analysis of the economic and environmental performance of the SHGC indicates that a 25% PVA fiber replacement ratio results in the best overall economic benefits and relatively low actual costs, although the effect of fiber hybridization on carbon emission indicators is not significant. This paper provides new ideas and a theoretical basis for designing low-cost SHGCs.

Abstract The efficacy of osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, has been evaluated in glioblastoma (GBM) through preclinical and clinical trials. However, the underlying mechanism of osimertinib-induced GBM cell death and the underlying resistance mechanism to osimertinib remains unclear. Here, we demonstrate that Osimertinib induces paraptosis in GBM cells, as evidenced by the formation of cytoplasmic vacuoles, accumulation of ubiquitinated proteins, and upregulation of endoplasmic reticulum (ER) stress markers like CHOP. Additionally, neither apoptosis nor autophagy was involved in the osimertinib-induced cell death. RNAseq analysis revealed ER stress was the most significantly downregulated pathway upon exposure to osimertinib. Consistently, pharmacologically targeting the PERK-eIF2α axis impaired osimertinib-induced paraptosis. Notably, we show that the expression of thyroid receptor-interacting protein 13 (TRIP13), an AAA+ATPase, alleviated osimertinib-triggered paraptosis, thus conferring resistance. Intriguingly, MK-2206, an AKT inhibitor, downregulated TRIP13 levels and synergized with Osimertinib to suppress TRIP13-induced high GBM cell growth in vitro and in vivo. Together, our findings reveal a novel mechanism of action associated with the anti-GBM effects of osimertinib involving ER stress-regulated paraptosis. Furthermore, we identify a TRIP13-driven resistance mechanism against Osimertinib in GBM and offer a combination strategy using MK-2206 to overcome such resistance.

Abstract Current induced spin-orbit torque (SOT) holds great promise for next generation magnetic-memory technology. Field-free SOT switching of perpendicular magnetization requires the breaking of in-plane symmetry, which can be artificially introduced by external magnetic field, exchange coupling or device asymmetry. Recently it has been shown that the exploitation of inherent crystal symmetry offers a simple and potentially efficient route towards field-free switching. However, applying this approach to the benchmark SOT materials such as ferromagnets and heavy metals is challenging. Here, we present a strategy to break the in-plane symmetry of Pt/Co heterostructures by designing the orientation of Burgers vectors of dislocations. We show that the lattice of Pt/Co is tilted by about 1.2° when the Burgers vector has an out-of-plane component. Consequently, a tilted magnetic easy axis is induced and can be tuned from nearly in-plane to out-of-plane, enabling the field-free SOT switching of perpendicular magnetization components at room temperature with a relatively low current density (~1011 A/m2) and excellent stability (> 104 cycles). This strategy is expected to be applicable to engineer a wide range of symmetry-related functionalities for future electronic and magnetic devices.

Abstract Background Immunogenic cell death (ICD), which releases danger-associated molecular patterns (DAMP) that induce potent anticancer immune response, has emerged as a key component of therapy-induced anti-tumor immunity. The aim of this work was to analyze whether the carbonic anhydrase IX inhibitor S4 can elicit ICD in glioma cells. Methods The effects of S4 on glioma cell growth were evaluated using the CCK-8, clonogenic and sphere assays. Glioma cell apoptosis was determined by flow cytometry. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of S4-treated cells were concentrated for the determination of HMGB1and HSP70/90 expression by immunoblotting. RNA-seq was performed to compare gene expression profiles between S4-treated and control cells. Pharmacological inhibition of apoptosis, autophagy, necroptosis and endoplasmic reticulum (ER) stress was achieved by inhibitors. In vivo effects of S4 were evaluated in glioma xenografts. Immunohistochemistry (IHC) was performed to stain Ki67 and CRT. Results S4 significantly decreased the viability of glioma cells and induced apoptosis and autophagy. Moreover, S4 triggered CRT exposure and the release of HMGB1 and HSP70/90. Inhibition of either apoptosis or autophagy significantly reversed S4-induced release of DAMP molecules. RNA-seq analysis indicated that the ER stress pathway was deregulated upon exposure to S4. Both PERK-eIF2α and IRE1α- XBP1 axes were activated in S4-treated cells. Furthermore, pharmacological inhibition of PERK significantly suppressed S4-triggered ICD markers and autophagy. In glioma xenografts, S4 significantly reduced tumor growth. Conclusions Altogether, these findings suggest S4 as a novel ICD inducer in glioma and might have implications for S4-based immunotherapy. Video Abstract

Abstract Mutation-based greybox fuzzing has been one of the most prevalent techniques for security vulnerability discovery and a great deal of research work has been proposed to improve both its efficiency and effectiveness. Mutation-based greybox fuzzing generates input cases by mutating the input seed, i.e., applying a sequence of mutation operators to randomly selected mutation positions of the seed. However, existing fruitful research work focuses on scheduling mutation operators, leaving the schedule of mutation positions as an overlooked aspect of fuzzing efficiency. This paper proposes a novel greybox fuzzing method, PosFuzz, that statistically schedules mutation positions based on their historical performance. PosFuzz makes use of a concept of effective position distribution to represent the semantics of the input and to guide the mutations. PosFuzz first utilizes Good-Turing frequency estimation to calculate an effective position distribution for each mutation operator. It then leverages two sampling methods in different mutating stages to select the positions from the distribution. We have implemented PosFuzz on top of AFL, AFLFast and MOPT, called Pos-AFL, -AFLFast and -MOPT respectively, and evaluated them on the UNIFUZZ benchmark (20 widely used open source programs) and LAVA-M dataset. The result shows that, under the same testing time budget, the Pos-AFL, -AFLFast and -MOPT outperform their counterparts in code coverage and vulnerability discovery ability. Compared with AFL, AFLFast, and MOPT, PosFuzz gets 21% more edge coverage and finds 133% more paths on average. It also triggers 275% more unique bugs on average.

Acute kidney injury (AKI) is a sudden loss of renal function with a high mortality rate and inflammation is thought to be the underlying cause. The phenylpropanoid components acteoside (ACT) and isoacteoside (ISO), which were isolated from Cistanche deserticola Y.C.Ma, have been reported to have preventive effects against kidney disorders. This study aimed to investigate the anti-inflammatory properties and protective mechanisms of ACT and ISO. In this investigation, kidney function was assessed using a semi-automatic biochemical analyzer, histopathology was examined using Hematoxylin-Eosin staining and immunohistochemistry, and the concentration of inflammatory cytokines was assessed using an enzyme-linked immunosorbent assay (ELISA) test. In addition, using Western blot and q-PCR, the expression of proteins and genes connected to the NF-κB signaling pathway in mice with lipopolysaccharide (LPS)-induced AKI was found. The findings showed that under AKI intervention in LPS group, ACT group and ISO group, the expression of Rela (Rela gene is responsible for the expression of NFκB p65 protein) and Tlr4 mRNA was considerably elevated (P

Chromatin-associated RNAs (caRNAs) form a relatively poorly recognized layer of the epigenome. The caRNAs reported to date are transcribed from the nuclear genome. Here, leveraging a recently developed assay for detection of caRNAs and their genomic association, we report that mitochondrial RNAs (mtRNAs) are attached to the nuclear genome and constitute a subset of caRNA, thus termed mt-caRNA. In four human cell types analyzed, mt-caRNAs preferentially attach to promoter regions. In human endothelial cells (ECs), the level of mt-caRNA–promoter attachment changes in response to environmental stress that mimics diabetes. Suppression of a non-coding mt-caRNA in ECs attenuates stress-induced nascent RNA transcription from the nuclear genome, including that of critical genes regulating cell adhesion, and abolishes stress-induced monocyte adhesion, a hallmark of dysfunctional ECs. Finally, we report increased nuclear localization of multiple mtRNAs in the ECs of human diabetic donors, suggesting many mtRNA translocate to the nucleus in a cell stress and disease-dependent manner. These data nominate mt-caRNAs as messenger molecules responsible for mitochondrial–nuclear communication and connect the immediate product of mitochondrial transcription with the transcriptional regulation of the nuclear genome.

Abstract The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naïve (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naïve TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers.

Steel-fiber reinforced polymer (FRP) composite bars (SFCBs) can enhance the controllability of damage in concrete structures; thus, studying the interfacial bonding between them is fundamental and a prerequisite for achieving deformation coordination and collaboration. However, research on the interfacial bonding performance between SFCBs and concrete remains inadequate. This study conducted central pullout tests on SFCB-concrete specimens with different concrete strengths (C30, C50, and C70), bar diameters (12, 16 and 20 mm), and hoop reinforcement constraints, analyzing variations in failure modes, bond-slip curves, bond strength, etc. Additionally, finite element simulations were performed using ABAQUS software to further validate the bonding mechanism of SFCB-concrete. The results showed that the failure mode of the specimens was related to the confinement effect on the bars. Insufficient concrete cover and lack of hoop restraint led to splitting failure, whereas pullout failure occurred otherwise. For the specimens with pullout failure, the interfacial damage between the SFCB and concrete was mainly caused by the surface fibers wear of the bar and the shear of the concrete lugs, which indicated that the bond of the SFCB-concrete interface consisted mainly of mechanical interlocking forces. In addition, the variation of concrete strength as well as bar diameter did not affect the bond-slip relationship of SFCB-concrete. However, the bond strength of SFCB-concrete increased with the increase of concrete strength. For example, compared with C30 concrete, when the concrete strength was increased to C70, the bond strength of the specimens under the same conditions was increased to 50–101.6%. In contrast, the bond strength of the specimens decreased by 13.29–28.71% when the bar diameter was increased from 12 to 14 mm. These discoveries serve as valuable references for the implementation of sustainable SFCB-reinforced concrete structures.

The design of high-performance polyimide (PI) films and understanding the relationship of the structure–dielectric property are of great significance in the field of the microelectronics industry, but are challenging. Herein, we describe the first work to construct a series of novel tert-butyl PI films (denoted as PI-1, PI-2, PI-3, and PI-4) based on a low-temperature polymerization strategy, which employed tetracarboxylic dianhydride (pyromellitic anhydride, 3,3′,4,4′-biphenyl tetracarboxylic anhydride, 4,4′-diphenyl ether dianhydride, and 3,3′,4,4′-benzophenone tetracarboxylic anhydride) and 4,4′-diamino-3,5-ditert butyl biphenyl ether as monomers. The results indicate that introducing tert-butyl branches in the main chain of PIs can enhance the free volume of the molecular chain and reduce the interaction between molecular chains of PI, resulting in a low dielectric constant. Particularly, the optimized PI-4 exhibits an excellent comprehensive performance with a high (5) wt% loss temperature (454 °C), tensile strength (117.40 MPa), and maximum hydrophobic angle (80.16°), and a low dielectric constant (2.90), which outperforms most of the results reported to date.

Abstract Grey-box fuzzing techniques have been widely used in software bug finding. In general, there are many decisions to make in the fuzzing process, including which code block in the target program should be explored first, which bytes of an input seed should be mutated to reach the target code block, and how to mutate the chosen input bytes. However, existing solutions usually rely on random exploration or certain heuristics to choose where and how to fuzz, which limits the efficiency of fuzzing. In this paper, we propose a novel solution CAMFuzz to guide the fuzzing process with explainable decisions in explainable artificial intelligence (XAI). First, we propose a dynamic weight adjustment algorithm, which considers both the difficulty of reaching a block and the number of unvisited blocks nearby, to find code blocks worthy to explore first. Second, we utilize a widely used local interpretation technique, i.e., class activation mapping (CAM), to recognize which part of an input seed should be mutated to reach a given target code block. Therefore, CAMFuzz can distinguish which part of code in the program is more important and which positions in the input file should be mutated first, in order to achieve a better code coverage and bug finding efficiency. Third, to further help the fuzzer increase fuzzing efficiency, we leverage a lightweight static program analysis to help the fuzzer identify magic values. We implement a prototype of CAMFuzz and evaluate it on 13 real-world programs (including 11 open source targets, 2 closed-source commercial products including a Microsoft component and Hancom Office) Results show that CAMFuzz outperforms state-of-the-art fuzzers in both code coverage and bug finding. To detail, CAMFuzz on average achieves 2.07 $$\times$$ × more bugs and 1.17 $$\times$$ × coverage improvements. In total, it found 19 previously unknown vulnerabilities, of which 6 have been assigned by CVE so far.

The aging properties of silicon rubber foam (SRF) were studied by using thermal-oxidative accelerated aging method, and the influence law of different aging time on cellular structure and properties of SRF was explored. The results showed that SRF materials with different densities had different cellular structure, and the large the density of SRF materials, the smaller cellular size, the thicker cellular wall and the larger the proportion of closed cell. In the process of thermal-oxidative aging, the cellular structure was destroyed with the increasing aging time. With the same aging time, the cellular structure of SRF materials with the higher density was destroyed more seriously. In addition, combined with the result of cellular microstructure and properties, it was found that the destruction of the cellular structure of SRF materials would lead to the increase of compression permanent deformation and stress loss rate.

Abstract Background Chinese materia medica processing is a distinguished and unique pharmaceutical technique in Traditional Chinese Medicine (TCM) used for reducing side effects, and increasing or even changing therapeutic efficacy of the raw herbs.Changes in the essential components induced by an optimized processing procedure are primarily responsible for the increased efficacy of medicinal plants.The kidney-yang invigorating effect of rice wine-steamed Cistancha deserticola (C. deserticola) was stronger than raw C. deserticola (CD). Methods A comparison analysis was carried out using the UPLC-Q-TOF-MSE with the UNIFI informatics platform to determine the influence of processing. In vitro studies were performed for the characterization of constituents as well as metabolites in vivo. The chemical components were determined in CD and its processed products. The multivariate statistical analyses were conducted to evaluate variations between them while OPLS-DA was used for pairwise comparison. Results The results of this study revealed considerable variations in phenylethanoid glycosides (PhGs) and iridoids after processing. A total of 97 compounds were detected in the extracts of CD and its processed product. PhGs having 4'-O-caffeoyl group in the 8-O-β-d-glucopyranosyl part, like acteoside, cistanoside C, campneoside II, osmanthuside decreased after being processed, while PhGs with 6'-O-caffeoyl group in the 8-O-β-d-glucopyranosyl part, such as isoacetoside, isocistanoside C, isocampneoside I, isomartynoside increased, especially in the CD-NP group. The intensity of echinacoside and cistanoside B whose structure possess 6'-O-β-d-glucopyranosyl moiety also increased. In in vivo study, 10 prototype components and 44 metabolites were detected in rat plasma, feces, and urine. The obtained results revealed that processing leads to the considerable variation in the chemical constituents of CD and affected the disposition of the compounds in vivo, and phase II metabolic processes are the key cascades of each compound and most of the metabolites are associated with echinacoside or acteoside. Conclusions This is the first global comparison research of raw and processed CD. These findings add to our understanding of the impact of CD processing and give important data for future efficacy investigations.

Abstract SOHO (small office/home office) routers provide services for end devices to connect to the Internet, playing an important role in cyberspace. Unfortunately, security vulnerabilities pervasively exist in these routers, especially in the web server modules, greatly endangering end users. To discover these vulnerabilities, fuzzing web server modules of SOHO routers is the most popular solution. However, its effectiveness is limited due to the lack of input specification, lack of routers’ internal running states, and lack of testing environment recovery mechanisms. Moreover, existing works for device fuzzing are more likely to detect memory corruption vulnerabilities.In this paper, we propose a solution ESRFuzzer to address these issues. It is a fully automated fuzzing framework for testing physical SOHO devices. It continuously and effectively generates test cases by leveraging two input semantic models, i.e., KEY-VALUE data model and CONF-READ communication model, and automatically recovers the testing environment with power management. It also coordinates diversified mutation rules with multiple monitoring mechanisms to trigger multi-type vulnerabilities. With the guidance of the two semantic models, ESRFuzzer can work in two ways: general mode fuzzing and D-CONF mode fuzzing. General mode fuzzing can discover both issues which occur in the CONF and READ operation, while D-CONF mode fuzzing focus on the READ-op issues especially missed by general mode fuzzing.We ran ESRFuzzer on 10 popular routers across five vendors. In total, it discovered 136 unique issues, 120 of which have been confirmed as 0-day vulnerabilities we found. As an improvement of SRFuzzer, ESRFuzzer have discovered 35 previous undiscovered READ-op issues that belong to three vulnerability types, and 23 of them have been confirmed as 0-day vulnerabilities by vendors. The experimental results show that ESRFuzzer outperforms state-of-the-art solutions in terms of types and number of vulnerabilities found.

In this paper, the filtering problem for the general time-invariant nonlinear state-observation system is considered. Our work is based on the Yau-Yau filtering framework developed by S.-T. Yau and the third author in 2008. The key problem of Yau-Yau filtering framework is how to compute the solution to forward Kolmogorov equation (FKE) off-line effectively. Motivated by the supervised learning in machine learning, we develop an efficient method to numerically solve the FKE off-line from the point of view of optimization. Specifically, for the off-line computation part, the computation of the solution to a FKE is reduced to computing a linear system of equations by making the temporal inverse transformation and the loss function optimization, and we store the results for the preparation of on-line computation. For the on-line computation part, the unnormalized density function is approximated by a complete polynomial basis, and then the estimation of the state is computed using the stored off-line data. Our method has the merits of easily implementing, real-time and memoryless. More importantly, it can be applicable for moderate-high dimensional cases. Numerical experiments have been carried out to verify the feasibility of our method. Our algorithm outperforms extended Kalman filter, unscented Kalman filter and particle filter both in accuracy and costing time.

In nuclear power plant (NPP), the digital control system introduced nuclear safety software, whose fault tolerance and reliability directly affect the safety of nuclear power plant facilities. Current manual, simulation and testing strategies all have limitations. An effective method to test the system with software plays an important role to ensure the safe operation of NPP. In this paper, a digital control system software test strategy based on real platform is proposed. Taking the RPS system as an example, this strategy analyzes the system function and software logic path characteristics, then identifies the system state by threshold boundary analyzing, and designs a test method based on the random combination of logical combination paths and parameter value intervals, and builds a real platform test environment. This paper has tested the typical functions of Pressurized water reactor (PWR) protection system. The test results show that the test strategy has significantly improved the coverage of paths and parameters. Compared with manual testing, test efficient has been improved obviously in this test platform. At present, this strategy solves the problem of the low efficiency in manual testing, low real-level in simulation testing, and the insufficient coverage in simple automated testing strategy. This strategy also provides good practice for the control system testing and lays the foundation for the reliability evaluation of the system and software.

Abstract A novel microwave-assisted sol–gel-hydrothermal method was employed to rapidly synthesize Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT) powders. The effects of reaction time on the structure, crystallinity, purity and morphology of the products were investigated. The results of XRD, FTIR, SEM and TEM indicated that BCZT powders could be obtained in even 60 min at a low synthesis temperature of 180 °C, which were well-crystallized with stoichiometric composition and uniform grain size (~ 85 nm). BCZT ceramic derived from the rapidly-synthesized powders had a dense microstructure and good electrical properties (εm = 9579, d33 = 496 pC/N, 2Pr = 25.22 µC/cm2, 2Ec = 7.52 kV/cm). The significant electrical properties were closely related to the high activity of the BCZT powders, resulting from the rapid microwave-assisted sol–gel-hydrothermal process.

Amorphous-nanocrystalline (a-nc) boron carbide thin films were prepared by chemical vapor deposition (CVD) by using ortho-carborane as a single-source precursor for inertial confinement fusion (ICF) application. The effects of deposition temperature (Tdep) and total pressure (Ptot) on chemical composition, microstructure, stoichiometry and morphology of the boron carbide films were investigated. The TEM results show that the structure of the film is mainly composed of amorphous boron carbide with dispersive nano-grains, which will be able to improve the mechanical properties of the film with relatively low roughness. The hardness of the (a-nc) boron carbide film obtained in this study reached 20.6 GPa, and roughness of 3.21 nm. The deposited films sized 0.2–1.9 μm in thickness with B/C atomic ratio ranged from 0.14 to 3.29. The deposition rate decreased with increasing deposition temperature and Ptot, while B/C ratio increased.

Background and Aim: Gliomas are the most common type of brain tumor in the world. Surgical resection is one of the most effective therapeutic methods in terms of patient prognosis. However, it is difficult for neurosurgeons and health-care providers to select which imaging technology to best support the procedure. These technologies included intraoperative magnetic resonance imaging (iMRI), intraoperative ultrasound (iUS), fluorescence guidance with 5-aminolevulinic acid (5-ALA), and intraoperative neuronavigation. Hence, in this study, we compared the gross total resection (GTR), postoperative complications within or outside of the central nervous system, and postoperative clinical improvement by multiple meta-analyses, which allows the integration of data through direct and indirect comparisons.Materials and Methods: The PubMed, Cochrane Library, Web of Science, Embase, China Knowledge Resource Integrated Database, and WanFang databases were searched for publications before April 2018. Randomized controlled trials, two-arm and three-arm prospective studies, and retrospective studies in patients who underwent surgical treatment for glioma were included. The most important outcome measures were the rates of GTR, postoperative complications, and clinical improvement. Results: In terms of GTR, iMRI (odds ratio [OR] = 5.70, 95% confidence interval [CI]: 3.40–9.60), iUS (OR = 2.70, 95% CI: 1.10–6.90), 5-ALA (OR = 2.40, 95% CI: 0.64–8.90), and neuronavigation (OR = 1.90, 95% CI: 1.20–3.10) were found to be more effective than conventional surgery. In addition, iUS (OR = 0.15, 95% CI: 0.04–0.52), iMRI (OR = 0.24, 95% CI: 0.14–0.43), and neuronavigation (OR = 0.34, 95% CI: 0.18–0.56) were more found to result in fewer complications than conventional surgery. Furthermore, patients' clinical improvement was better with iMRI (OR = 8.10, 95% CI: 3.00–25.00), iUS (OR = 4.90, 95% CI: 0.76–33.00), and neuronavigation (OR = 2.60, 95% CI: 1.00–7.20) than with conventional surgery. Conclusions: The developed ranking probability table indicated that iMRI was superior in terms of the GTR and clinical improvement, while iUS was the least likely to result in postoperative complications. Hence, it was concluded that iMRI or iUS is the most advantageous imaging modality.

The majority of human CD8 cytotoxic T lymphocytes express αβ T‐cell receptors that recognize peptide–MHC class I complexes. Considerable attention has been devoted to TCR β repertoires, but study of TCR α chains has been limited. To gain a better understanding of the features of CDR3α and CDR3β in paired samples, we comprehensively analyzed 776 unique paired αβ TCR CDR3 regions in this study. We found that (I) the CDR3 length among paired αβ TCRs had a fairly narrow distribution due to random assortment of CDR3 length in alpha and beta chains; (II) nucleotide deletions among CDR3 regions were positively correlated with insertions in both α and β TCRs; (III) the CDR3 loops of both α and β chains contained an abundance of charged/polar residues and the CDR3 base regions contained a conserved motif; and (IV) the occurrence of Gly was CDR3 length‐ and position‐dependent in both chains, whereas the frequency of Ser at positions 106 and 107 was positively correlated with CDR3 length in TCR β. Overall, the amino acids in CDR3 loop regions were significantly different between TCR α and β, which suggests a distinct role for each chain in the recognition of antigen–MHC complexes. Here, we have provided detailed information on CDR3 in paired TCRs expressed on human CD8+ T cells and established the basis of a reference set for αβ TCR repertoires in healthy humans.

A qualitative and quantitative study was performed on the carbonization temperature (TC) and carbonization time (tC) with respect to the microstructure and growth rate (Rg) of a 3C-SiC epitaxial layer on Si (111) substrates by carbonization via laser chemical vapor deposition (LCVD). The results showed that the density and size of the voids depended strongly on TC. The voids were sealed, and thin films were formed continuously and uniformly after a carbonization time of 6 min at TC = 1200 °C. Rg was also dependent on TC, and increased from 0.43 to 1.35μm·h−1 with increases in TC from 1000 to 1200 °C. These deposition rates are 10 to 100 times greater than those of observed for conventional CVD methods.

Abstract Background Glioblastoma (GBM) is an extremely deadly form of brain cancer with limited treatment options and thus novel therapeutic modalities are necessary. Histone deacetylase inhibitors (HDACi) have demonstrated clinical and preclinical activities against GBM. (Silent mating type information regulation 2 homolog, Sirt1) abbreviated as Sirtuin 1, has been implicated in GBM. We explored the activity of the Sirt1 activator SRT2183 in glioma cell lines in terms of biological response. Methods The effects of SRT2183 on glioma cell growth and neurosphere survival were evaluated in vitro using the CCK-8, clonogenic and neurosphere assays, respectively. Glioma cell cycle arrest and apoptosis were determined by flow cytometry. SRT2183-induced autophagy was investigated by detection of GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) puncta, conversion of the nonlipidated form of LC3 (LC3-I) to the phosphatidylethanolamine-conjugated form (LC3-II). Acetylation of STAT3 and NF-κB in SRT2183-treated glioma cells was examined using immunoprecipitation. The expression levels of anti-apoptotic proteins were assayed by immunoblotting. Results SRT2183 suppressed glioma cell growth and destroyed neurospheres in vitro. Furthermore, SRT2183 induced glioma cell cycle arrest and apoptosis, accompanying by upregulation of the pro-apoptotic Bim and downregulation of Bcl-2 and Bcl-xL. Notably, ER stress was triggered in glioma cells upon exposure to SRT2183 while the pre-exposure to 4-PBA, an ER stress inhibitor, significantly antagonized SRT2183-mediated growth inhibition in glioma cells. In addition, SRT2183 induced autophagy in glioma cells and pharmacological modulation of autophagy appeared not to affect SRT2183-inhibited cell growth. Of interest, the acetylation and phosphorylation of p65 NF-κB and STAT3 in glioma cells were differentially affected by SRT2183. Conclusions Our data suggest the ER stress pathway is involved in SRT2183-mediated growth inhibition in glioma. Further investigation in vivo is needed to consolidate the data.

The spin mixing conductance g↑↓ of a ferromagnetic and a nonmagnetic (NM) layer characterizes the transport efficiency of spin current through the interface. Exploration of the relationship between g↑↓ and structural parameters such as the lattice orientation of the NM layer is critical to design effective spintronics devices. Here, the spin mixing conductance of two types of single oriented Pt and Ni81Fe19 (Py) was studied experimentally, with the method of spin pumping. The obtained g↑↓ for Pt (100)/Py and Pt (111)/Py bilayers is 8.6 ± 0.9 nm−2 and 10.8 ± 1.6 nm−2, respectively, revealing the fact that the crystalline orientation of the metallic NM layer has no prominent impact on g↑↓, which is consistent with the theoretical prediction.

Understanding the molecular mechanisms in wheat response to nitrogen (N) fertilizer will help us to breed wheat varieties with improved yield and N use efficiency. Here, we cloned TaLAMP1-3A, -3B, and -3D, which were upregulated in roots and shoots of wheat by low N availability. In a hydroponic culture, lateral root length and N uptake were decreased in both overexpression and knockdown of TaLAMP1 at the seedling stage. In the field experiment with normal N supply, the grain yield of overexpression of TaLAMP1-3B is significantly reduced (14.5%), and the knockdown of TaLAMP1 was significantly reduced (15.5%). The grain number per spike of overexpression of TaLAMP1-3B was significantly increased (7.2%), but the spike number was significantly reduced (19.2%) compared with wild type (WT), although the grain number per spike of knockdown of TaLAMP1 was significantly decreased (15.3%), with no difference in the spike number compared with WT. Combined with the agronomic data from the field experiment of normal N and low N, both overexpression and knockdown of TaLAMP1 inhibited yield response to N fertilizer. Overexpressing TaLAMP1-3B greatly increased grain N concentration with no significant detrimental effect on grain yield under low N conditions; TaLAMP1-3 B is therefore valuable in engineering wheat for low input agriculture. These results suggested that TaLAMP1 is critical for wheat adaptation to N availability and in shaping plant architecture by regulating spike number per plant and grain number per spike. Optimizing TaLAMP1 expression may facilitate wheat breeding with improved yield, grain N concentration, and yield responses to N fertilizer.

The temporal permeability and damage evolutions of low-permeability sandstone cores during triaxial and long-term dissolution experiments were measured using a triaxial-flow system. Three triaxial experiments were performed on sandstone cores having initial permeability ranging from 78×10−18 m2 to 120×10−18 m2. Two sets of long-term dissolution experiments were conducted on cracked sandstone cores. All dissolution experiments were performed at room temperature and using a 10 g/L H2SO4 and 0.2 g/L H2O2 input solution. Permeability evolution was determined using Darcy’s law. The cores experienced an average increase of 25% in permeability in the dissolution experiment and 900%~1500% increase at the end of the experiment. The dissolution was fairly homogeneous during the long-term experiments whether on the 1 mm scale or the 10 μm scale. The relationship between damage and permeability was speculated and its correlation coefficient has been proved to be close to 1. These results suggest that hydraulic fracturing works well in permeability increase in low-permeability sandstone reservoir.

Salt processing, which involves steaming with salt water, directs herbs into the kidney channel. After being salt processed, kidney invigorating effects occur. However, the underlying mechanism of this method remains elusive. The compounds monotropein, rubiadin, and rubiadin 1-methyl ether are the major effective components of Morinda officinalis How. To clarify the pharmacokinetics and tissue distribution of these three compounds, we employed liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to determine the contents of the three components in rat plasma and tissues. Separation was achieved on an Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm, Waters). Formic acid aqueous solution (0.1%; A) and acetonitrile (containing 0.1% formic acid; B) were used as the mobile phase system with a programmed elution of 0∼5 min with 70% A and then 5∼7 min with 60% A. All analytes were measured with optimized multiple reaction monitoring (MRM) in negative ion mode. Geniposide and 1,8-dihydroxyanthraquinone were used as the internal standards (IS). The linear ranges were 1.2∼190, 1.3∼510, and 0.047∼37.5 μg/mL, respectively. Compared with the Morinda officinalis without wood (MO) group, the Cmax and AUC0-t parameters of rubiadin and rubiadin 1-methyl ether elevated remarkably for the salt-processed Morinda officinalis (SMO) groups, which indicates that steaming by salt could increase the bioavailability of rubiadin and rubiadin 1-methyl ether. The Tmax for monotropein is shorter (0.5 h) in SMO groups than that in MO group, which means that monotropein was quickly absorbed in the SMO extract. Moreover, the contents of three compounds in the small intestine were the highest.

The perpendicular magnetic anisotropy (PMA) and perpendicular exchange bias (PEB) have been investigated in a CoPt/spacer/FeMn heterostructure by inserting Ta and Pt as spacer layers, respectively. First, we show that strong PMA can be obtained in (111)-oriented A1-CoPt single layer and CoPt/FeMn bilayer films on MgO (111) substrates. Then we demonstrate that the Ta and Pt spacer layers have largely different effects on the PMA and PEB of the CoPt/spacer/FeMn films. By increasing the thickness of the Ta spacer layer to 1 nm, the PMA and PEB drastically decrease. While, in the case of Pt, the PMA and PEB increase first, then slightly decrease. When the Pt spacer layer is 1 nm, a value of 85 Oe of the long-range PEB still can be obtained. The possible mechanisms were discussed to explain the different trends of PMA and PEB. Since Ta and Pt are the generally used materials in the spintronics, our study provides a piece of information for the control of the magnetic anisotropy and exchange bias in the current-induced magnetization switching of ferromagnet without external magnetic field.

Using the yellowfin tuna (Thunnusalbacares,YFT)longline fishing catch data in the open South China Sea (SCS) provided by WCPFC, the optimum interpolation sea surface temperature (OISST) from CPC/NOAA and multi-satellites altimetric monthly averaged product sea surface height (SSH) released by CNES, eight alternative options based on Bayes classifier were made in this paper according to different strategies on the choice of environment factors and the levels of fishing zones to classify the YFT fishing ground in the open SCS. The classification results were compared with the actual ones for validation and analyzed to know how different plans impact on classification results and precision. The results of validation showed that the precision of the eight options were 71.4%, 75%, 70.8%, 74.4%, 66.7%, 68.5%, 57.7% and 63.7% in sequence, the first to sixth among them above 65% would meet the practical application needs basically. The alternatives which use SST and SSH simultaneously as the environmental factors have higher precision than which only use single SST environmental factor, and the consideration of adding SSH can improve the model precision to a certain extent. The options which use CPUE’s mean ± standard deviation as threshold have higher precision than which use CPUE’s 33.3%-quantile and 66.7%-quantile as the threshold

Ultrahigh-performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight tandem mass spectrometry (Q/TOF-MS) in the MS/MS mode and UPLC coupled with triple quadrupole mass spectrometry (QqQ-MS) using the multiple reaction monitoring (MRM) mode were used to make a qualitative and quantitative analysis of twelve bile acids in Bile Arisaema. The fragmentation pathway of twelve bile acids was proposed. The quantification method showed a good linearity over a wide concentration range (R2 > 0.99), repeatability (RSD

The hydrogen absorption/desorption processes of (111)-textured and normal palladium (Pd) thin films of thickness ranging from 8 to 48 nm are investigated using X-ray diffractometry. The one-dimensional expansion of Pd lattice due to the substrate clamping is observed at the low hydrogen composition phase while both out-of-plane and in-plane expansions are detected at the high hydrogen composition phase. Accordingly, using a biaxial Poisson’s ratio, an anisotropic expansion factor is proposed for describing such phenomenon quantitatively and the hydrogen composition dependence on this factor is investigated.

BiFeO3/TiN/MgO (001) films have been prepared by magneton sputtering, where TiN serves as a conductive under layer. X-ray diffraction profiles and cross-sectional transmission electron microscopy images reveal that not only (001)-epitaxial BiFeO3 films are obtained, but also both tetragonal and rhombohedral phases co-exist in BiFeO3 films. Their crystallographic relationship is shown as following: tetragonal-BiFeO3 (001) [100]//TiN (001) [100]//MgO (001) [100] and rhombohedral-BiFeO3 (001) [100]//TiN (001) [100]//MgO (001) [100]. Besides, an oxidized TiN layer (∼ 20 nm) has also been detected between BiFeO3 and TiN layers and its formation may originate from oxygen inter-diffusion from BiFeO3 layer. Despite of the existence of the oxidized TiN layer, it does not affect the epitaxial growth of BiFeO3 films. On the other hand, the coercivity electric field obtained in ferroelectric loop of BiFeO3 is greatly enhanced to 49 MV/cm due to the existence of oxidized TiN layer.

As environmental requirements become more stringent, the liquid carbon dioxide blasting system is one of the non-explosive blasting technologies that, with low tensile stress energy, will replace the chemical explosive blasting technology, and the impact pressure characteristic of high-pressure fluid is a crucial factor in the process of rock breaking. To further investigate the impact and pressure attenuation characteristics of high-pressure fluid during the phase transition of liquid carbon dioxide blasting system, the pressure curves of high-pressure fluid in liquid carbon dioxide blasting systems at different distances were measured in the laboratory. Based on the mechanism analysis of phase transition kinetics, the initial jet velocity of the four experiments was calculated, and the rationality of results was verified by the Bernoulli equation. The general expression of the positive phase pressure−time function was proposed, and the idealized impact pressure curve can be divided into five stages. The impact pressure field of the liquid carbon dioxide blasting system can be divided into three areas at different distances: the explosive jet impact zone, the jet edge zone and the shock wave action zone, and the pressure−contrast distance fitting equation of the liquid carbon dioxide blasting system were obtained.

We report intrinsic spin decay length of an antiferromagnetic insulator. We found that at an antiferromagnetic/ferromagnetic interface, a spin current generated by spin pumping is strongly suppressed by two-magnon scattering. By eliminating the two-magnon contribution, we discovered that the characteristic length of spin decay in polycrystalline NiO changes by two orders of magnitude through the paramagnetic to antiferromagnetic transition. The spin decay length in the antiferromagnetic state is around 100 nm, which is an order of magnitude longer than that previously believed. These results provide a crucial piece of information for the fundamental understanding of the physics of spin transport.

The CuxSi1−x thin films have been successfully fabricated by pulsed laser deposition (PLD). The influences of laser energy fluency (I0) and deposition temperature (Td) on the phase structure were investigated. The results show that Cu deposited on Si (001) at I0 = 0.5-2.0 J/cm2, and η”-Cu3Si formed on Si (111) at I0 = 1.0-2.0 J/cm2. The films were consisted of Cu, η’-Cu3Si, ε-Cu15Si4 and δ-Cu0.83Si0.17 at Td = 100-500 °C on Si (001). The films were the single phase of η-Cu3Si at Td = 700 °C. In the case of Si (111), the phase structures transformed from Cu to Cu + η’-Cu3Si to η’-Cu3Si to η’-Cu3Si + η-Cu3Si with the increasing of Td. Rectangular grains were formed on Si (001), whereas triangular grains on Si (111). Cu (001) film was epitaxially grown on Si (001) at I0 = 1.5 J/cm2 and Td = 20 °C. η-Cu3Si (001) epitaxial layer was formed on Si (111) at I0 = 1.5 J/cm2 and Td = 700 °C. The epitaxial relationships of Cu (001)[100]//Si (001)[110] and η-Cu3Si (001)[-110]//Si (111)[11-2] were identified.

In this study, we demonstrated the chemical vapor deposition (CVD) of vertically standing molybdenum disulfide (MoS2) nanosheets, with an unconventional combination of molybdenum hexacarbonyl (Mo(CO)6) and 1,2-ethanedithiol (C2H6S2) as the novel kind of Mo and S precursors respectively. The effect of the distance between the precursor’s outlet and substrates (denoted as d) on the growth characteristics of MoS2, including surface morphology and nanosheet structure, was investigated. Meanwhile, the relationship between the structure characteristics of MoS2 nanosheets and their catalytic performance for hydrogen evolution reaction (HER) was elucidated. The formation of vertically standing nanosheets was analyzed and verified by means of an extrusion growth model. The crystallinity, average length, and average depth between peak and valley (Rz) of MoS2 nanosheets differed depending on the spatial location of the substrate. Good crystalized MoS2 nanosheets grown at d = 5.5 cm with the largest average length of 440 nm, and the highest Rz of 162 nm contributed to a better HER performance, with a respective Tafel slope and exchange current density of 138.9 mV/decade, and 22.6 μA/cm2 for raw data (127.8 mV/decade and 19.3 μA/cm2 for iR-corrected data).

The study was aimed to evaluate the potential of existing genotypes of Jerusalem artichoke (Helianthus tuberosus L.) as biomass feedstock for ethanol production. We investigated the biomass productivity and chemical composition of twenty-six Jerusalem artichoke clones grown in a semi-arid region of China. Jerusalem artichoke was demonstrated to be a sustainable feedstock for bioethanol production. All structural and non-structural carbohydrates in whole plant of Jerusalem artichoke could be 5000 L/ha. The above-ground biomass of Jerusalem artichoke could be a promising feedstock for cellulosic ethanol. The ethanol potential yield from cellulose and hemicellulose in aboveground biomass were 1821 to 5930 L/ha, contributing 29.8-66.4% of the total ethanol yield, which could be as high as that from switchgrass and sweet sorghum stem. Large variation among the investigated genotypes for carbohydrates makes it possible to select suitable clones to be used in bioethanol production in semiarid regions. Clones HB-3, HEN-3, IM-1, SC-1, SHX-3, SX-2 and ZJ-2 yielded tuber total soluble sugar higher than 4.0 t/ha. Clones BJ-4, HUB-2, HUN-2, QH-1, SD-2 and SHH-1 produced more than 5.0 t/ha cellulose and hemicellulose in above-ground biomass. Clones BJ-4 and HUB-2 have the highest ethanol potential based on structural carbohydrates. These clones were promising material if used as biofuel feedstock in this growth condition.

PURPOSE:OLC1 was recently identified to be a potential oncogene. However, the role of OLC1 in human esophageal cell carcinoma (ESCC) is unknown. The aim of this study was therefore to evaluate the expression of OLC1 in human ESCC from normal, premalignant, and malignant lesions, and to clarify the mechanisms by which OLC1 contributes to the progression of ESCC. EXPERIMENTAL DESIGN:Two hundred and fourteen paired ESCC specimens, and an independent set from 28 ESCC patients, were used to analyze the correlation between OLC1 expression and the pathological characteristics of tumors using immunohistochemistry. Stable OLC1-overexpressing and OLC1-interfering esophageal cancer cells were established and a series of experimental methods were used to investigate the biological functions and mechanisms of action of OLC1. RESULTS:We showed that OLC1 was overexpressed in 145 of 214 (67.8%) of human ESCC specimens, compared with in only 59 of 214 (27.57%) paired adjacent normal tissues (P