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Trimethylamine (TMA) is a harmful gas that exists ubiquitously in the environment; therefore, the sensitive and specific monitoring of TMA is necessary. In this work, we prepared ultrasensitive flexible sensors for TMA detection based on single-walled carbon nanotubes (SWCNTs) and olfactory receptor-derived peptides (ORPs) on low-cost plastic substrates. A novel bending connection method was developed by intentionally bending the interdigitated electrodes with SWCNTs to form a three-dimensional structure during the ORP-connection process, leading to the exposure of more modification sites. The method showed ∼4.7-fold more effective connection amount of the ORPs to SWCNTs compared to the conventional flat-condition connection method. The flexible ORP-SWCNT sensors could significantly improve the limit of detection for gaseous TMA from the reported lowest limit of 10 parts per quadrillion (ppq) to 0.1 ppq. The flexible ORP sensors also exhibited excellent sensitivity to vaporized TMA standards and TMA generated by different kinds of foods under different bending conditions. The results showed that the bending connection method in this work was effective for ultrasensitive flexible ORP sensors and their associated applications.

Flexible electronics have gained attention with their unique ability to withstand stress deformations. However, stress makes significant impact on the electrical performance of the flexible devices. It is commonly believed that the stress imposed on the flexible device is only related to the bending curvature. Our study shows that the actual stress imposed on the device is not only related to the bending radius but also closely related to the device dimension. In this study, the effective stress of the device layer as well as the stress distributions are investigated, with the fundamental flexible diodes as representative examples. Flexible single-crystalline silicon [Formula: see text]-[Formula: see text]-[Formula: see text] diodes are fabricated and measured under different bending curvature conditions. Then the dominant affecting factor of the flexible diodes with bending stress is extracted. 3D finite-element method (3D-FEM) stress distribution modeling is also employed to analyze the stress distributions and demonstrate that the effective stress of the device layer is closely and proportionally related to the device dimension. Furthermore, theoretical calculations are conducted to verify the FEM results and quantitatively show the relation between the stress and the dimension of the flexible devices. The analysis provides a guideline in the design of flexible electronics under bending conditions.

Failure analysis (FA) becomes increasingly crucial for semiconductor industries with the scale-down and larger integration of devices. In order to overcome the limitation of traditional optical resolution for FA techniques, this article proposed an effective method of precise positioning of circuit defect based on localized probing technique, nano-probing and electron beam absorbed current (EBAC). Open circuit, short circuit and gate/capacitor oxide defects were the most common failures in IC manufactures, therefore representative examples based on these failures were employed to illustrate the analysis procedure and effectiveness of the proposed method. Scanning electron microscope (SEM), focused ion beam (FIB) and transmission electron microscope (TEM) results were presented to verify the accuracy of the positioning. It was demonstrated that the proposed precise positioning method was able to accurately locate the defect position, and was useful for determining the failure mechanism as well. The method showed great potential for improving the success rate of FA for semiconductor devices.

The DC and AC performances of proton radiated Silicon-Germanium (SiGe) Heterojunction Bipolar Transistors (HBTs) with different emitter areas at liquid nitrogen temperature (77 K), room temperature and heating hotplate (393 K) were presented in this work. Performance dependence on the emitter area and temperature was investigated. Results showed that SiGe HBTs with a large emitter area had more damage by proton radiation. Furthermore, the SiGe HBTs showed better tolerance to proton radiation at extreme temperatures than at room temperature. To reveal the underlying mechanism, the radiated SiGe HBTs were modeled based on the device structure and parameters. The electron density, Shockley–Read–Hall (SRH) recombination and carrier mobility were extracted from the device model and demonstrated to have major impacts on the performance dependence of the radiated SiGe HBTs. The results provide useful guidance for the application of SiGe HBTs at extreme environments.

Single-cell analysis of proteins is critical to gain precise information regarding the mechanisms that dictate the heterogeneity in cellular phenotypes and their differential response to internal and external stimuli. However, tools that allow sensitive and easy measurement of proteins in individual cells are still limited. The emerging semiconductor-based bioelectronics may provide a new approach to overcome the challenges in this field, however its utility in single-cell protein analysis has not been explored. In this study, we investigated multiple protein detection in single cells by MoS

Failure analysis (FA) was encountered as a ion charging risk when using focused ion beam to insert extra test pads for mixed signal integrated circuits (IC) on silicon on insulator (SOI). To overcome this challenge, and to precisely locate the open circuit defect, this paper described an effective non-destructive FA method based on dynamic InGaAs photon emission microscopy and schematic/layout analysis to determine the open circuit type and position. Nano-probing and electron beam absorbed current was used to located the precise location of the open circuit defect. Two typical samples of mixed signal IC on SOI were used (Samples 1 and 2, with extra and missing emission spots, respectively) to illustrate the analysis procedure and effectiveness for the proposed method. Scanning electron microscope results were presented to verify the accuracy of this method. It was demonstrated that the proposed method was able to accurately determine failure of open circuit efficiently without microprobe for mixed signal IC on SOI.

Two-dimensional (2D) layered semiconductor materials have emerged as prospective channel materials in flexible thin-film field effect transistors (TFTs) recently because of their unique electrical and mechanical characteristics. Meanwhile, high-quality ceramics, with outstanding dielectric property and fabrication process compatible with low-cost flexible substrates, have become one of the best candidates of gate dielectric layers in flexible TFTs. In this work, 2D MoS

This paper proposes a flexible passive filter and summarizes the design rules of a flexible filter from the perspective of physical design methods. Compared with the filter design method of lumped structure, the distributed structure can reduce the effect of stress and transfer the stress of flexible deformation from the device itself to the substrate, and under a certain range of stress, the device can maintain good performance. In this paper, the above viewpoints are well verified by simulation experiments. A distributed structure is used to design the passive filter, which reduces the stress damage and stress induced performance impact of the device, and provides theoretical guidance for enhancing the reliability design of the flexible filter.

Interacting with proteins is a crucial way for long noncoding RNAs (lncRNAs) to exert their biological responses. Here we report a high throughput strategy to characterize lncRNA interacting proteins in vivo by combining tobramycin affinity purification and mass spectrometric analysis (TOBAP-MS). Using this method, we identify 140 candidate binding proteins for lncRNA highly upregulated in liver cancer (HULC). Intriguingly, HULC directly binds to two glycolytic enzymes, lactate dehydrogenase A (LDHA) and pyruvate kinase M2 (PKM2). Mechanistic study suggests that HULC functions as an adaptor molecule that enhances the binding of LDHA and PKM2 to fibroblast growth factor receptor type 1 (FGFR1), leading to elevated phosphorylation of these two enzymes and consequently promoting glycolysis. This study provides a convenient method to study lncRNA interactome in vivo and reveals a unique mechanism by which HULC promotes Warburg effect by orchestrating the enzymatic activities of glycolytic enzymes., Here the authors present a quantitative proteomics strategy to identify long noncoding RNA (lncRNA)-binding proteins and demonstrate its application by characterizing the lncRNA HULC (highly upregulated in liver cancer), which is shown to interact with glycolytic enzymes and modulate their activity.

Flexible integrated circuits have gained a lot of attention in recent years for their emerging applications in wearable electronics. Flexible thin-film transistors (TFTs) with low-costs and high-performance are highly desirable as essential and fundamental elements for most flexible applications. In this paper, we fabricate single-crystalline silicon nanomembrane (SiNM)-based TFTs with anodized aluminum oxide (AAO) as a dielectric material on glass and flexible plastic substrates. Good quality AAO was obtained on plastic substrates at room temperature. Atomic force microscopy (AFM)was used for the surface morphology of the AAO gate dielectric layers on different substrates (i.e. glass, polyethylene terephthalate (PET), and SU-8 coated PET). The electrical characteristics of the AAO gate dielectric layers on different substrates were also analyzed with metal–insulator–metal capacitors. The SiNMs were processed with a complementary metal oxide semiconductor (CMOS) compatible semiconductor process (e.g. photolithography, ion implantation, thermal annealing, reactive ion etching, metal evaporation, etc), and then transferred to the substrates with AAO/aluminum stack layers. The performance of the transistors on glass and plastic substrates was characterized. Compared with the TFT fabricated on a glass substrate, the TFT fabricated directly on a PET substrate had lower performance due to poor surface roughness. For optimization of the surface roughness, the PET was modified with a coating of SU-8 photoresist. In this way, the TFT had properties close to that on a glass substrate. AAO that can be manufactured at room temperature provides a simple and low-cost solution for high-performance flexible single-crystalline SiNM TFTs.

Acetone commonly exists in daily life and is harmful to human health, therefore the convenient and sensitive monitoring of acetone is highly desired. In addition, flexible sensors have the advantages of light-weight, conformal attachable to irregular shapes, etc. In this study, we fabricated high performance flexible silicon nanowires (SiNWs) sensor for acetone detection by transferring the monocrystalline Si film and metal-assisted chemical etching method on polyethylene terephthalate (PET). The SiNWs sensor enabled detection of gaseous acetone with a concentration as low as 0.1 parts per million (ppm) at flat and bending states. The flexible SiNWs sensor was compatible with the CMOS process and exhibited good sensitivity, selectivity and repeatability for acetone detection at room temperature. The flexible sensor showed performance improvement under mechanical bending condition and the underlying mechanism was discussed. The results demonstrated the good potential of the flexible SiNWs sensor for the applications of wearable devices in environmental safety, food quality, and healthcare.

The mammalian target of rapamycin complex 2 (mTORC2) plays critical roles in various biological processes. To better understand the functions of mTORC2 and the underlying molecular mechanisms, we established a stable cell line with reduced Rictor, a specific component in mTORC2, and investigated the quantitative changes of the cellular proteome. As a result, we observed that 101 proteins were down-regulated and 50 proteins were up-regulated in Rictor knockdown cells. A protein-protein interaction network regulated by Rictor/mTORC2 was established, showing that Rictor/mTORC2 was involved in various cellular processes. Intriguingly, gene ontology analysis indicated that the proteome regulated by Rictor/mTORC2 was significantly involved with cell adhesion. Rictor knockdown affected the expressions of multiple cell adhesion associated molecules, e.g. integrin α-5 (ITGA5), transforming growth factor beta-1-induced transcript 1 protein (TGFB1I1), lysyl oxidase homologue 2 (LOXL2), etc. Further study suggested that Rictor/mTORC2 may regulate cell adhesion and invasion by modulating the expressions of these cell adhesion molecules through AKT. Taken together, this study maps the proteome regulated by Rictor/mTORC2 and reveals its role in promoting renal cancer cell invasion through modulating cell adhesion and migration.

A novel method of fabricating flexible thin-film transistor based on single-crystalline Si nanomembrane (SiNM) with high-k Nb2O5–Bi2O3–MgO (BMN) ceramic gate dielectric on a plastic substrate is demonstrated in this paper. SiNMs are successfully transferred to a flexible polyethylene terephthalate substrate, which has been plated with indium-tin-oxide (ITO) conductive layer and high-k BMN ceramic gate dielectric layer by room-temperature magnetron sputtering. The BMN ceramic gate dielectric layer demonstrates as high as ∼109 dielectric constant, with only dozens of pA current leakage. The Si–BMN–ITO heterostructure has only ∼nA leakage current at the applied voltage of 3 V. The transistor is shown to work at a high current on/off ratio of above 104, and the threshold voltage is ∼1.3 V, with over 200 cm2/(V s) effective channel electron mobility. Bending tests have been conducted and show that the flexible transistors have good tolerance on mechanical bending strains. These characteristics indicate that th...

Background Protein kinase C ζ (PKCζ), an isoform of the atypical protein kinase C, is a pivotal regulator in cancer. However, the molecular and cellular mechanisms whereby PKCζ regulates tumorigenesis and metastasis are still not fully understood. In this study, proteomics and bioinformatics analyses were performed to establish a protein-protein interaction (PPI) network associated with PKCζ, laying a stepping stone to further understand the diverse biological roles of PKCζ. Methods Protein complexes associated with PKCζ were purified by co-immunoprecipitation from breast cancer cell MDA-MB-231 and identified by LC-MS/MS. Two biological replicates and two technical replicates were analyzed. The observed proteins were filtered using the CRAPome database to eliminate the potential false positives. The proteomics identification results were combined with PPI database search to construct the interactome network. Gene ontology (GO) and pathway analysis were performed by PANTHER database and DAVID. Next, the interaction between PKCζ and protein phosphatase 2 catalytic subunit alpha (PPP2CA) was validated by co-immunoprecipitation, Western blotting and immunofluorescence. Furthermore, the TCGA database and the COSMIC database were used to analyze the expressions of these two proteins in clinical samples. Results The PKCζ centered PPI network containing 178 nodes and 1225 connections was built. Network analysis showed that the identified proteins were significantly associated with several key signaling pathways regulating cancer related cellular processes. Conclusions Through combining the proteomics and bioinformatics analyses, a PKCζ centered PPI network was constructed, providing a more complete picture regarding the biological roles of PKCζ in both cancer regulation and other aspects of cellular biology. Electronic supplementary material The online version of this article (10.1186/s12953-018-0134-8) contains supplementary material, which is available to authorized users.

Background: Y-box binding protein 1 (YB1) is a multifunctional protein involved in many processes related to cancer progression and metastasis. Methods: In this study, we constructed YB1 knockdown stable renal cell carcinoma (RCC) cell line 786-0. The gene expression profile of 786-0 was performed by DNA microarray analysis to identify genes that were regulated by YB1. Real-time PCR and western blotting were used to test the genes and proteins expression. Transforming growth factor-β (TGF-β) activity was detected by dual-luciferase reporter assay. Cell adhesion assay was used to determine RCC cell adhesion ability. Results: Pathway analysis revealed that YB1 knockdown influenced cell adhesion molecules (CAMs). We further verified four genes (CLDN4, NRXN3, ITGB8, and VCAN) related to CAMs by real-time PCR, and confirmed that YB1 regulated the expression of ITGB8 in RCC. Functional assays demonstrated that knockdown of YB1 significantly inhibited the cell adhesion of 786-0 cells in vitro. In addition, YB1 affected TGF-β activation. Conclusion: Our study demonstrated that YB1 modulated the adhesion ability of renal cell carcinoma cells by regulating ITGB8 and TGF-β.

Recently, the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with major impact on public health. Novel methods that enable fast and efficient detection of the virus and the associated biomarkers, such as SARS-CoV-2 antibodies, may provide alterative opportunities for early diagnosis, disease status monitoring, and the development of vaccines. Here, we report the fabrication of a functionalized MoS2-field effect transistor (FET) for sensitive and quantitative detection of antibodies against SARS-CoV-2 spike protein receptor binding domain (S-RBD) in vaccinated serum specimens. The device was modified by SARS-CoV-2 S-RBD fusion protein on the surface and enabled rapid detection of SARS-CoV-2 antibodies. In addition, an on-chip calibration method was established for quantitative measurement. Furthermore, this method was applied to measure the levels of S-RBD antibodies in serum specimens from vaccinated donors. The devices showed no response to negative control samples from individuals who did not receive vaccination, suggesting the high specificity of this method. This study illustrated the successful fabrication of S-RBD functionalized MoS2-FET with potential clinical applications to facilitate vaccine development and efficacy evaluation.

A dielectric ceramics/TiO

Barium stannate (BaSnO3, BS) and silver composite thin films are deposited on flexible polyethylene terephthalate (PET) substrates by magnetron sputtering. The effects of structural design on electrical and optical properties of the BS/Ag/BS tri-layer flexible thin films are investigated systematically. The BS layers can enhance the transmittance significantly, due to the fact that reflection of light from the Ag layer and PET substrate can be suppressed by BS layers. The tri-layer thin films show the high figure of merit of 16.66 × 10−3 Ω−1 and the large commutation quality factor of 197, while the average optical transmittance in the visible light range is above 84% and the sheet resistance is 10.52 Ω/sq. In addition, the flexible tri-layer thin films show outstanding mechanical flexibility, adhesion to PET substrate and stability at high temperature.

A novel method of fabricating flexible thin-film transistor based on single-crystalline Si nanomembrane (SiNM) with high- k Nb

Supplemental information. (DOC 78Â kb)

Renal cell carcinoma (RCC) is a common urologic tumor and the third leading cause of death among urological tumors. Recent studies demonstrate that RCC tumors are more heavily infiltrated by lymphocytes than other cancers. However, the exact roles played by CD4 + T cells in RCC proliferation remain unknown. In this study, we cocultured RCC cells with CD4 + T cells. Stable knockdown of YBX1 in RCC cells was constructed. The effects of CD4 + T cells, TGFβ1 and YBX1 on RCC cells were investigated using cell viability assays. In situ RCC nude mouse model was used to observe the tumor growth. The potential mechanisms of CD4 + T cells and YBX1 in RCC cells proliferation were explored by qRT-PCR and western blot. Expression of CD4, Foxp3 and TGFβ1 in RCC were quantified by immunohistochemical staining. The results indicated that CD4, Foxp3 and TGFβ1 were significantly up-regulated in RCC tissues. Human clinical sample and in vitro cell lines studies showed that RCC cells had better capacity than its surrounding normal kidney epithelial cells to recruit the CD4 + T cells. In vivo mouse model studies were consistent with the results by in vitro cell lines studies showing infiltrating T cells enhanced RCC cell proliferation. qRT-PCR and western blot exhibited that CD4 + T cells could enhance RCC cell proliferation via activating YBX1/HIF2α signaling pathway. Furthermore, CD4 + T cells functioned through inducing TGFβ1 expression. In a word, infiltrating CD4 + T cells promoted TGFβ1 expression in both RCC and T cells and regulated RCC cells proliferation via modulating TGFβ1/YBX1/ HIF2α signals.

Hepatocellular carcinoma (HCC) is one of the leading causes of mortality related to cancer all over the world. To better understand the molecular mechanisms of HCC metastasis, we analyzed the proteome of three HCC cell lines with different metastasis potentials by quantitative proteomics and bioinformatics analysis. As a result, we identified 378 cellular proteins potentially associated to HCC metastasis, and constructed a highly connected protein-protein interaction (PPI) network. Functional annotation of the network uncovered prominent pathways and key roles of these proteins, suggesting that the metabolism and cytoskeleton biological processes are greatly involved with HCC metastasis. Furthermore, the integrative network analysis revealed a rich-club organization within the PPI network, indicating a hub center of connections. The rich-club nodes include several well-known cancer-related proteins, such as proto-oncogene non-receptor tyrosine kinase (SRC) and pyruvate kinase M2 (PKM2). Moreover, the differential expressions of two identified proteins, including PKM2 and actin-related protein 2/3 complex subunit 4 (ARPC4), were validated using Western blotting. These two proteins were revealed as potential prognostic markers for HCC as shown by survival rate analysis.

Linearity characteristics of common-emitter (CE) and common-base (CB) configuration SiGe HBTs are analyzed and compared under different matching, bias and frequency conditions. Impedance matching is demonstrated to have significant effect on the configuration-dependent linearity characteristics. Moreover, with source and load impedance matched for maximum output power, CE and CB configurations not only show different power gain relation but also different linearity characteristics dependence on frequency. Theoretical expressions show good agreement of the RF linearity property for simulation and experimental results. Further dc bias study reveals that both higher power-gain and better linearity can be obtained from the CB than the CE configuration under certain bias and operation conditions. A potential tradeoff between the two configurations in terms of linearity and power gain is also demonstrated.