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The relationship between matter properties and their atomic-scale structures is a challenging investigation. For relaxor ferroelectrics, correlating the relaxor mechanisms on the atomic scale to properties is still ambiguous. Here, the correlation between the atomic-scale structure and strain performance of 0.94 Bi 0.5 Na 0.5 TiO 3 -0.06BaTiO 3 (94BNT-6BT) and 0.93 Bi 0.5 Na 0.5 TiO 3 -0.06BaTiO 3 -0.01BaZrO 3 (93BNT-6BT-1BZ) is reported. The δ Ti-Bi/Na displacement vector map based on the annular dark field (ADF) scanning transmission electron microscopy (STEM) image demonstrates the coexistence of tetragonal (T) and rhombohedral (R) phases of the resulting ceramics, and BZ doping increases the proportion of the T phase. Furthermore, the enhanced annular bright field (eABF) STEM image demonstrates that BZ doped ceramics exhibit obvious oxygen octahedral tilt. The oxygen octahedral tilt increased gradually from the domain wall to the inner place of the nanodomain, indicating a regional consistency, which results in enhancement of the relaxor performance and stain property. This study opens exciting opportunities to the design of relaxor ferroelectrics with large strain for high-displacement actuator applications.

Using ZnO nanowires as needle anodes in gas discharge is helpful for maintaining continuous discharge with a relatively low voltage. It is necessary that the ZnO nanowires are far enough apart to guarantee no electric field weakening and that the nanowire anodes are easy to assemble together with the discharging devices. An AC/DC electric-field-assisted wet chemical method is proposed in this paper. It was used to grow ZnO nanowires directly on discharging devices. The nanowires covered the whole electrode in the case in which only a DC field was applied. Moreover, the tips of the nanowires were scattered, similar to the results observed under the application of AC fields. The average distance between the tips of the highest nanowires was approximately equal to 4 μm, which almost meets the requirement of gas discharge. The research concerning growing ZnO nanowires directly on PCBs shown that, at the current time, ZnO nanowires on PCBs did not meet the requirements of gas discharge; however, in this study, the parameters regarding ZnO nanowire growth were established.

As a crucial kind of pervasive gene, long noncoding RNAs (lncRNAs) are abundant and key players in brain function as well as numerous neurological disorders, especially ischemic stroke. The mechanisms underlying ischemic stroke include angiogenesis, autophagy, apoptosis, cell death, and neuroinflammation. Inflammation plays a vital role in the pathological process of ischemic stroke, and systemic inflammation affects the patient's prognosis. Although a great deal of research has illustrated that various lncRNAs are closely relevant to regulate neuroinflammation and microglial activation in ischemic stroke, the specific interactional relationships and mechanisms between lncRNAs and neuroinflammation have not been described clearly. This review aimed to summarize the therapeutic effects and action mechanisms of lncRNAs on ischemia by regulating inflammation and microglial activation. In addition, we emphasize that lncRNAs have the potential to modulate inflammation by inhibiting and activating various signaling pathways, such as microRNAs, NF-κB and ERK., Competing Interests: Yongli Pan, Qingzheng Jiao, Wei Wei and Tianyang Zheng should be considered co-first authors. The authors declare that they have no competing interests., (© 2021 Pan et al.)

Stem cells have attracted increasing research interest in the field of regenerative medicine due to their unique abilities to differentiate into multiple cell lineages. Label-free, real-time, and long-term monitoring for stem cell differentiation is requisite in studying directional differentiation and development mechanisms for tissue engineering applications, but a great challenge because of the rigorous demands for sensitivity, stability and biocompatibility of devices. In this article, a label-free and real-time monitoring approach using a zinc oxide (ZnO) nanorod field effect transistor (FET) is proposed to detect cell traction forces (CTFs) exerted by cells on underlying substrates. The ZnO nanorod FET with the approach of difference-frequency lock-in detection achieves high sensitivity, good stability, and excellent biocompatibility, by which real-time and long-term (over 20 days) monitoring of cellular mechanical changes in osteogenic differentiation of mesenchymal stem cells (MSCs) is successfully achieved. We also employ electrical impedance monitoring using microelectrode array chips and microscopic observation to investigate cell migration and nodular aggregation behaviors of MSCs in osteogenic differentiation. Various biochemical assays including alkaline phosphatase (ALP), osteopontin expression and alizarin red staining are utilized to verify osteogenic differentiation of MSCs. We propose a combination of cell traction force measurement, impedance measurement and microscopic observation to provide multimodal profiling of cell morphology, and cellular biomechanical and electrophysiological phenotypes, which can track cellular dynamics in stem cell development and help to deeply understand the mechanism of osteogenic differentiation.

The ability to precisely deliver molecules into single cells while maintaining good cell viability is of great importance to applications in therapeutics, diagnostics, and drug delivery as it is an advancement toward the promise of personalized medicine. This paper reports a single-cell individualized electroporation method with real-time impedance monitoring to improve cell perforation efficiency and cell viability using a microelectrode array chip. The microchip contains a plurality of sextupole-electrode units patterned in an array, which are used to perform in situ electroporation and real-time impedance monitoring on single cells. The dynamic recovery processes of single cells under electroporation are tracked in real time via impedance measurement, which provide detailed transient cell states and facilitate understanding the whole recovery process at the level of single cells. We define single-cell impedance indicators to characterize cell perforation efficiency and cell viability, which are used to optimize electroporation. By applying the proposed electroporation method to different cell lines, including human cancer cell lines and normal human cell lines individually, optimum stimuli are determined for these cells, by which high transfection levels of enhanced green fluorescent protein (EGFP) plasmid into cells are achieved. The results validate the effectiveness of the proposed single-cell individualized electroporation/transfection method and demonstrate promising potential in applications of cell reprogramming, induced pluripotent stem cells, adoptive cell therapy, and intracellular drug delivery technology., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Effective induction methods and in situ monitoring are essential for studying the mechanism of biological responses in stem cell differentiation. This article proposes an induction method incorporating electrical stimulation under an inhomogeneous field with single-cell impedance monitoring for studying osteogenic differentiation of mesenchymal stem cells (MSCs) using a microchip. The microchip contains an array of sextupole-electrode units for implementing a combination of controllable electrical stimulation and single-cell impedance measurements. MSCs are inducted to osteogenic differentiation under electrical stimulation using quadrupole electrodes and single-cell impedances are monitored in situ using a pair of microelectrodes at each unit center. The proposed microchip adopts an array design to monitor a number of MSCs in parallel, which improves measurement throughput and facilitates to carry out statistic tests. We perform osteogenic differentiation of MSCs on the microchip with and without electrical stimulation meanwhile monitoring single-cell impedance in real time for 21 days. The recorded impedance results show the detailed characteristic change of MSCs at the single-cell level during osteogenic differentiation, which demonstrates a significant difference between the conditions with and without electrical stimulation. The cell morphology and various staining analyses are also used to validate osteogenesis and correlate with the impedance expression. Correlation analysis of the impedance measurement, cell morphology, and various staining assays proves the great acceleration effect of the proposed electrical stimulation on osteogenic differentiation of MSCs. The proposed impedance method can monitor the dynamic process of cell development and study heterogeneity of stem cell differentiation at the single-cell level.

Retraction of 'Microelectrochemical cell arrays for whole-cell currents recording through ion channel proteins based on trans-electroporation approach' by Tianyang Zheng et al., Analyst, 2020, 145, 197-205.

Correction for 'Microelectrochemical cell arrays for whole-cell currents recording through ion channel proteins based on trans-electroporation approach' by Tianyang Zheng, et al., Analyst, 2020, DOI: 10.1039/c9an01737b.

Electrical stimulation (ES) as an easy and effective inducing method has been widely used in induction differentiation of stem cells, e.g. osteogenic differentiation of mesenchymal stem cells (MSCs) for bone healing and bone tissue therapies. However, the micro-effect of an inhomogeneous electric field has rarely been investigated for ES in induction differentiation, and conventionally used ex situ assays may preclude accurate assessment due to variation from cell inoculation and treatments. Here, a novel electrical stimulation method with a microelectrode array chip is proposed for osteogenic differentiation of MSCs. The electric field applied onto the MSCs by the microelectrode array is designed similarly with a natural aggregation distribution of differentiated MSCs. The proposed ES method accelerates osteoblast proliferation and differentiation in the electrode array region and generates a larger amount of mineralized deposits, which are assayed via in situ alizarin red staining and morphology observation as well as immunocytochemistry. In addition, this method allows a direct in situ assessment to compare the osteogenic differentiation of MSCs with and without ES on a single chip to avoid culture environment difference. The method provides a fundamental platform for investigating induced differentiation of stem cells and allows integration with multifunctional cell assays to achieve in situ tracking for the differentiation process of stem cells.

High electrostability and long life-time of planar chip technology are crucial for electrophysiological measurements such as ionic current recording through ion channel proteins embedded in biological cell membrane. In this paper, we propose a novel planar microchip integrated with microelectrochemical cell array toward to a feasible solution for ion channel screening with high resolution and long life-time. In order to reduce the interference from the leakage currents, a synthetic lipid bilayer is applied to form a high sealing resistance. The whole-cell electrical access can be constructed via electroporating the lipid bilayer in close proximity to the cell membrane. Parameters of electroporation including amplitude and time scale are firstly optimized by using parallel electroporation to the lipid bilayers. In this approach, individual cells can be trapped to the target positions by applying dielectrophoresis (DEP) manipulation. Poly(ethylene glycol) (PEG) is employed with low concentration to facilitate the closed contact between the cells and the lipid bilayer to increase the efficiency of the whole-cell mode construction. Through this chip based method, stable current recordings through inward rectifier potassium (Kir) ion channels embedded in rat basophilic leukemia (RBL-1) cell membrane are achieved with high electrical sealing resistance (over 1 GΩ). In addition, without need for complex fluidic connections, this method allows for an easy operation and further miniaturization of the measuring system.

Ginsenoside Rg1 (GS Rg1) is a glycosylated triterpenoid saponin extracted from Panax ginseng. We aim to investigate the impact of GS Rg1 on protein aggregation and inflammatory response in a cerebral ischemia/reperfusion (I/R) injury model. Rats were administered different doses of GS Rg1 (10, 20, or 40 mg/kg/day) or nimodipine (1 mg/kg/day) for 5 consecutive days. Cerebral I/R injury was induced by middle cerebral artery occlusion for 2 h followed by a 22 h reperfusion period. Next, we examined the differences in infarct volume and neurological deficit via TTC staining and Longa's scoring, respectively. Furthermore, the differences in protein aggregates, proteasome, IκBα and NF-κB in the cerebral cortices were investigated through western blotting. The distribution of ubiquitin, proteasome and NF-κB in the neocortex were examined through immunohistochemistry. Pro-inflammatory cytokines were measured using ELISA and proteasome activity was determined by fluorometric peptidaseassay. Treatment with GS Rg1 40 mg/kg resulted in a significantly lower infarct volume and improved the neurological deficit score as well as the histological appearance compared to the control I/R group (P < 0.05). GS Rg1 treatment resulted in significantly lower proinflammatory cytokine expressions and suppression of the nuclear translocation of NF-κB as well as the phosphorylation of IκBα (P < 0.01). Finally, GS Rg1 treatment decreased the proteasomal activity and protein aggregate accumulation in brain tissues (P < 0.01). Our results confirm the neuroprotective function of GS Rg1 at 40 mg/kg. This effect may be attributed to a decrease in ubiquitinated aggregates and a suppression of the inflammatory response after I/R insult., (Copyright © 2019. Published by Elsevier B.V.)

Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults. Despite continuous improvements in diagnosis and therapeutic method, the prognosis is still far away from expectations. The invasive phenotype of GBM is the main reason for the poor prognosis. Epithelial-mesenchymal transition (EMT) is recognized as a participator in this invasive phenotype. Resveratrol, a natural plant-derived compound, is reported to be able to regulate EMT. In the present study, we used TGF- β 1 to induce EMT and aimed to evaluate the effect of resveratrol on EMT and to explore the underline mechanism in GBM. Western blotting was used to detect the expression of EMT-related markers, stemness markers, and Smad-dependent signaling. Wound healing assay and transwell invasion assay were performed to evaluate the migratory and invasive ability of GBM cells. Gliosphere formation assay was used to investigate the effect of resveratrol on the ability of self-renewal. Xenograft experiment was conducted to examine the effect of resveratrol on EMT and Smad-dependent signaling in vivo . Our data validated that resveratrol suppressed EMT and EMT-associated migratory and invasive ability via Smad-dependent signaling in GBM cells. We also confirmed that resveratrol obviously inhibited EMT-induced self-renewal ability of glioma stem cells (GSCs) and inhibited EMT-induced cancer stem cell markers Bmi1 and Sox2, suggesting that resveratrol is able to suppress EMT-generated stem cell-like properties in GBM cells. Furthermore, we also showed the inhibitory effect of resveratrol on EMT in xenograft experiments in vivo . Overall, our study reveals that resveratrol suppresses EMT and EMT-generated stem cell-like properties in GBM by regulating Smad-dependent signaling and provides experimental evidence of resveratrol for GBM treatment.

These days, multiplex assay with diverse functions on a single chip has become more and more imperative for biological cell research. Multipoint and multistep manipulation for single cells on a chip plays a significant role for cell characterization, immunoassays, and rare cell isolation, etc. In this article, a novel dielectrophoresis (DEP)-based manipulation method is proposed to flexibly move and position cells on a chip via applying various electrical signals onto microelectrodes. By modulating phases and amplitudes of alternating current (ac) signals applied onto the microelectrodes, single cells can be controllably moved from one position to another along diverse directions on a chip. Quantitative analysis is conducted for position and direction controls via simulation, which are validated through experiments. With this flexible manipulation method, single-cell biophysical parameters can be estimated in situ by moving the cell, and as an example, single HeLa and MCF-7 cells are measured. This method allows an efficient and flexible transportation of single cells in lab-on-a-chip systems and provides a fundamental platform for multioriented and multipoint manipulation. The chip is easy to scale up by means of array design for more multifunctional cell assays.