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Primary hippocampal neuronal cells were used to establish cell model of cerebral ischemia under oxygen-glucose deprivation (OGD) treatment. After the cell model was pre-treated with short hairpin (sh)-circ_NLRP1 or mmu-miR-199b-3p inhibitor, LDH release and cell apoptosis were detected by LDH kit and TUNEL staining, respectively, while the expression of NLRP3 pyroptosis-related makers was analyzed through immunofluorescence (IF) assay and Western blot, respectively. The binding sites between circ_NLRP1 and mmu-miR-199b-3p were predicted and further validated by Dual Luciferase Reporter assay. Additionally, mitogen-activated protein kinase (MAPK) pathway was also analyzed by means of Western blot assay. Neuronal cells under OGD conditions released less lactate dehydrogenase (LDH) and showed less apoptosis status by silencing circ_NLRP1. In addition, gasdermin D (GSDMD)-N immunofluorescence staining showed weaker fluorescence intensity and decreased expression of pyroptosis-related mediators. We further found that mmu-miR-199b-3p-inhibitor could alter the effects of sh-circ_NLRP1 on hippocampal neuronal cells. In addition, in this process, extracellular signal-regulated kinase (ERK)/EGR1 pathway was also significantly affected. In conclusion, OGD stimulation induced neuronal damage and pyroptosis through enhancing circ_NLRP1 expression and further downregulating mmu-miR-199b-3p levels. The present study provided a novel insight for understanding the potential mechanism of ischemia-induced neuronal damage and for developing new drugs for treating brain ischemia damage., Graphical Abstract

An on-site detection strategy is reported based on dual-color SiO2@quantum dot (QD)–integrated lateral flow immunoassay (LFA) strip to realize the quantitative and simultaneous detection of C-reactive protein (CRP) and procalcitonin (PCT) in serum. The dual-color SiO2@QD nanotags with monodispersity and excellent luminescence were synthesized using polyethyleneimine-mediated electrostatic adsorption of dense red CdSe/ZnS-COOH (excitation/emission 365/625 nm) or green CdSe/ZnS-COOH (excitation/emission 365/525 nm) QDs on the surface of 180 nm SiO2 spheres and were conjugated with anti-PCT and anti-CRP monoclonal antibodies, as stable and fluorescent-enhanced QD nanotags in the LFA system. The use of SiO2@QDs with two different fluorescent signals caused the sensitivity and specificity of the multiplex LFA system. As a result, the proposed assay provided a wide logarithmic determination range with a CRP quantitative range of 0.5–103 ng/mL and PCT quantitative range of 0.05–103 ng/mL. The limits of detection (LODs) of CRP and PCT reached 0.5 and 0.05 ng/mL, respectively. The SiO2@QD-based LFA showed great potential as rapid detection tool for the simultaneous monitoring of CRP and PCT in serum sample.

Continued reduction in transistor size can improve the performance of silicon integrated circuits (ICs). However, as Moore's Law approaches physical limits, high-performance growth in silicon ICs becomes unsustainable, due to challenges of scaling, energy efficiency, and memory limitations. The ultra-thin layers, diverse band structures, unique electronic properties, and silicon compatible processes of two-dimensional (2D) materials create the potential to consistently drive advanced performance in ICs. This review presents the potential of fusing 2D materials with silicon ICs to minimize the challenges in silicon ICs, and to create technologies beyond the von Neumann architecture. It discusses the killer applications for 2D materials in logic and memory devices to ease scaling, energy efficiency bottlenecks, and memory dilemmas encountered in silicon ICs. The fusion of 2D materials allows the creation of all-in-one perception, memory and computation technologies beyond the von Neumann architecture to enhance system efficiency and remove computing power bottlenecks. Progress on the 2D ICs demonstration is summarized, as well as the technical hurdles it faces in terms of wafer-scale heterostructure growth, transfer, and compatible integration with silicon ICs. Finally, the promising pathways and obstacles to the technological advances in ICs due to the integration of 2D materials with silicon is presented. This article is protected by copyright. All rights reserved.

Early diagnosis of cancer biomarkers is the key to guiding treatments and improving the survival rate of patients. Herein, we report a novel surface-enhanced resonance Raman scattering (SERRS)-based lateral flow immunoassay (LFIA) for quantitative and ultra-sensitive analysis of alpha-fetoprotein (AFP). Gold nanorods (AuNRs) were fabricated to be in resonance with 785 nm laser excitation, that is, the excitation level that can maximize SERRS activity. The AuNRs were modified with 5,5′-dithiobis(2-nitrobenzoic acid), bovine serum albumin (BSA), and AFP detection antibody successively as the SERRS nanotags for the LFIA system. Modification of the BSA layer guaranteed good stability and biocompatibility of the SERRS nanotags in complex samples. The SERRS-LFIA strip for AFP detection showed a low detection limit of 9.2 pg mL−1 and a broad detection range from 10 pg mL−1 to 500 ng mL−1. By comparison, the detection limit of the proposed assay is about 100 and 10 times lower than those of the Au nanoparticle-based SERS-strip and conventional enzyme-linked immunosorbent assay, respectively. Moreover, the potential clinical applications of the assay were evaluated by detecting 10 actual serum samples. Results showed 100% accuracy based on the clinical tests.

The parasitic parameters and equivalent electrical model of differential dielectric-cavity through-silicon via (DDC-TSV) array on traditional low-resistivity silicon (LRSi) are proposed in this letter. TSV plugs are placed in the dielectric-cavity etched on LRSi. Each analytical formula in the model is established as the fuction of various physical geometries. The resistance–inductance–capacitance–conductance model and S-parameters of the DDC-TSV array are constructed by the Advanced Design System (ADS), which is verified by the 3-D full-wave electromagnetic solver High Frequency Simulator Structure (HFSS). Simulation results of the ADS and HFSS accord well with each other with frequencies up to 100 GHz, which shows good accuracy of the proposed model.

Accurate detection of mutiple biomarkers in unprocessed blood via lateral flow immunoassay (LFA) strips remains challenging. Herein, we reported a novel surface-enhanced Raman scattering (SERS)-based LFA strip for ultrasensitive and simultaneous analysis of dual infection biomarkers by using functionalized Fe3O4@Au magnetic nanoparticles (MNPs). Antibody-modified Fe3O4@Au MNPs were designed as SERS nanotags and efficient enrichment tool. The target infection biomarkers were quickly captured and enriched from the blood sample by Fe3O4@Au nanotags. After washing to remove impurities, Fe3O4@Au nanotags acted as high-performance SERS reporters for quantitative detection of the target in the LFA strip. Through this strategy, the proposed Fe3O4@Au based LFA allowed quantified analysis of target infection biomarkers in unprocessed blood samples with the limits of detection of 0.1 ng/mL and 0.01 ng/mL for serum amyloid A (SAA) and C-reactive protein (CRP), respectively. By comparison, the proposed assay for SAA and CRP was 100-fold and 1000-fold more sensitive than standard colloidal gold strip by using the same antibodies, respectively. This magnetic SERS strip also exhibited excellent stability, specificity, and selectivity for complex samples and could be used as an effective tool for infectious disease diagnostics.

The present study aimed to investigate the effect of avicularin on rheumatoid arthritis (RA) in vitro, and additionally explore the molecular mechanism. To perform this investigation, an in vitro model of RA was established by treatment of the human RA synovial MH7A cell line with tumor necrosis factor-α (TNF-α). MH7A cells were then treated with various concentrations (10, 30, 100 and 300 µM) of avicularin. Then, the levels of inflammatory factors [interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP)-1 and MMP-13] were measured by ELISA. Cell viability and apoptosis were detected using an MTT assay and flow cytometry, respectively. In addition, the expression levels of genes and proteins were determined reverse transcription quantitative polymerase chain reaction and western blot analysis. The results of the present study indicated that avicularin significantly decreased the levels of inflammatory factors (IL-1β, IL-6, IL-8, MMP-1 and MMP-13), previously increased by TNF-α, in a dose-dependent manner. Concurrently, avicularin inhibited the mRNA and protein expression levels of iNOS and COX-2 increased by TNF-α. It was also identified that TNF-α administration significantly promoted MH7A cell viability and inhibited cell apoptosis, and avicularin treatment dose-dependently inhibited MH7A cell viability and induced cell apoptosis. In addition, these data suggested that avicularin prevented the activation of the mitogen-activated protein kinase kinase (MEK)/nuclear factor kappa light-chain-enhancer of activated B-cells (NF-κB) pathway activated by TNF-α. Taken together, these results demonstrated that avicularin may inhibit the inflammatory response, prevent cell viability and induce apoptosis in human RA synovial cells through preventing the activation of the MEK/NF-κB pathway.

In this letter, the parasitic inductance of tapered ground-signal-ground (GSG) type through-silicon via (TSV) pair used in high speed three-dimensional integrated circuits (3-D ICs) are proposed. Rigorous closed-form formulas of the inductance, exploiting loop and partial inductances, are derived based on the geometric information with frequency up to 20 GHz, which also cover the cylinder and GS-mode TSVs. The proposed models are in good agreement with the 3-D electromagnetic (EM) simulator and measurement results with maximum errors of 8%.

In this paper, a facile electrochemical alloying–dealloying technique was performed in aqueous media to prepare a nanoporous platinum (Pt) electrode with high sensitivity for glucose sensing. A homogeneous Pt–Cu alloy was electrochemically deposited on a glassy carbon electrode at room temperature, and then Cu in the alloy was selectively dissolved by electrochemical method from the Pt–Cu alloy resulting in the nanoporous platinum film with a higher surface area. A roughness factor of the electrode was determined from the ratio of the true area to the geometric area, and it was up to 184. This nanoporous platinum exhibits high stability and remarkable catalytic activity for glucose oxidation in pH 7.0 PBS. It is also resistant toward poisoning by some common interfering species such as uric acid and p-acetamidophenol. Under the optimal experimental conditions, the nanoporous platinum film responded to glucose with a good linear dependence in the range from 1.00 × 10 −5 to 8.14 × 10 −3 M and the detection limit was 7.75 × 10 −6 M (S/N = 3).

In this paper, closed-form expression of the parasitic capacitance of the tapered Through-Silicon Via (TSV) is proposed, which also cover the cylindrical TSV when the slop wall angle is 90°. The comparison between the results of Ansoft Q3D verification and Matlab calculation are made. It shows that the root mean square error is less than 6.10%, over a wide range of the bottom radius and the height of tapered TSV, and the oxide thickness, therefore, the expression presented proves to be accurate.

The azocalix[4]arene film modified glassy carbon electrode was established for the convenient and sensitive detection of four DNA bases (guanine, adenine, thymine and cytosine). Field emission scanning electron microscopy, attenuated total reflectance-FTIR and X-ray photoelectron spectroscopy were used to characterize the film. The azocalix[4]arene film exhibited excellent electrocatalytic activity toward the oxidation of all bases. Well-separated voltammetric peaks were obtained among guanine, adenine, thymine and cytosine, which lead to the feasibility for the simultaneous determination of all of them in a mixture without separation or pretreatment. Linear calibration curves were obtained from 0.125 to 200.0 μM for adenine, 0.125 to 175.0 μM for guanine, 2.50 to 650.0 μM for thymine, and 2.50 to 650.0 μM for cytosine. This sensor also exhibits good stability, reproducibility and long lifetime.

Accurate analytical models for the strain and stress in silicon induced by annular Through-silicon-via (TSV) are proposed. Finite element method (FEM) is used for the model verification. It is shown that errors for the strain and stress models are respectively less than 6.6% and 6.8% for various metal and dielectric materials. Based on the analytical model of stress, keep-out-zones (KOZs) are also evaluated for pMOS and nMOS, as the stress is parallel and perpendicular to transistor channel. Annular TSVs with various materials induce KOZs of less than 6.6μm. W exhibits the best thermo-mechanical performance with KOZ=0.