Bioinspired Engineering of Fillable Gradient Structure into Flexible Capacitive Pressure Sensor Toward Ultra-High Sensitivity and Wide Working Range.

Tactile sensing is required for electronic skin and intelligent robots to function properly. However, the dielectric layer's poor structural compressibility in conventional pressure sensors results in a limited pressure sensing range and low sensitivity. To solve this issue, a flexible pressure sensor with a crocodile-inspired fillable gradient structure is provided. The fillable gradient structure and grooves in the pressure sensor accommodate the deformed microstructure that permits the enhancement of the media layer compressibility via COMSOL finite element simulation and optimization. The pressure sensor exhibits a high sensitivity of up to 0.97 k Pa-1 (0-4 kPa), a wide pressure detection range (7 Pa-380 kPa), and outstanding repeatability. The sensor can detect Morse code, robotic grabbing, and human motion monitoring. As a result, flexible sensors with a bionic fillable gradient structure pave the way for wearable devices and offer a novel method for achieving highly precise tactile perception.

Suppression of miR-147b contributed to H37Rv-infected macrophage viability and migration in tuberculosis in vitro.

BACKGROUND: Tuberculosis (TB) is a severe infectious disease. It was reported that microRNAs played important roles in tuberculosis. However, the role of miR-147b in the disease remained unveiling. METHODS: Tuberculosis cell model was established using macrophage THP-1 cells infected with H37Rv strain. RT-qPCR was first for examination of miR-147b relative expression. Cell viabilities were then measured with MTT. Cell transfection was to interfere the relative expression of miR-147b or C11orf87 in infected cells. RT-qPCR was adopted to confirm the transfection efficiency. Luciferase assay verified the binding sites between miR-147b and C11orf87. Migration was examined by scratch and relative protein expression of EMT biomarkers and phosphorylation of Pi3K and AKT were assessed via Western blot. RESULT: MiR-147b expression was higher and cell viability decreased in H32Rv-THP-1 cells. Cell viability was shown higher after miR-147b downregulation. Luciferase assay confirmed the binding. RT-qPCR found C11orf87 expression was lower in the H32Rv-THP-1 cells. MTT suggested that cell viability fell with the decrease of C11orf87 in infectious cells. Moreover, when H32Rv-THP-1 cells were co-transfected with miR-147b inhibitor and si-C11orf87, cell viability, migration and EMT and activation of Pi3K/AKT pathway was partially reversed compared with mere downregulation of miR-147b. CONCLUSION: miR-147b might regulate macrophage proliferation and migration through targeting C11orf87 via Pi3K/AKT pathway in Tuberculosis in vitro, which calls for in-depth inter-cellular researches and animal researches to further support that miR-147b/C11orf87 axis might be a potential therapeutic target for the molecular treatment of Tuberculosis in the future.

Tactile corpuscle-inspired piezoresistive sensors based on (3-aminopropyl) triethoxysilane-enhanced CNPs/carboxylated MWCNTs/cellulosic fiber composites for textile electronics.

Recently, wearable electronic products and gadgets have developed quickly with the aim of catching up to or perhaps surpassing the ability of human skin to perceive information from the external world, such as pressure and strain. In this study, by first treating the cellulosic fiber (modal textile) substrate with (3-aminopropyl) triethoxysilane (APTES) and then covering it with conductive nanocomposites, a bionic corpuscle layer is produced. The sandwich structure of tactile corpuscle-inspired bionic (TCB) piezoresistive sensors created with the layer-by-layer (LBL) technology consists of a pressure-sensitive module (a bionic corpuscle), interdigital electrodes (a bionic sensory nerve), and a PU membrane (a bionic epidermis). The synergistic mechanism of hydrogen bond and coupling agent helps to improve the adhesive properties of conductive materials, and thus improve the pressure sensitive properties. The TCB sensor possesses favorable sensitivity (1.0005 kPa-1), a wide linear sensing range (1700 kPa), and a rapid response time (40 ms). The sensor is expected to be applied in a wide range of possible applications including human movement tracking, wearable detection system, and textile electronics.

Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice.

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of ß-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin in human colorectal cancer cells, we found that E-cadherin, a protein that regulates cell-cell adhesion, epithelial-mesenchymal transition and metastasis, was almost completely lost in Dcn(-/-) mouse intestine, and loss of decorin and E-cadherin accelerated colon cancer cell growth and invasion in Dcn(-/-) mice. However, increasing decorin expression in colorectal cancer cells attenuated cancer cell malignancy, including inhibition of cancer cell proliferation, promotion of apoptosis and importantly, attenuation of cancer cell migration. All these changes were linked to the regulation of E-cadherin by decorin. Moreover, overexpression of decorin upregulated E-cadherin through increasing of E-cadherin protein stability as E-cadherin messenger RNA and promoter activity were not affected. Co-immunoprecipitation assay showed a physical binding between decorin and E-cadherin proteins. Taken together, our results provide direct evidence that decorin-mediated inhibition of colorectal cancer growth and migration are through the interaction with and stabilization of E-cadherin.

2-Cyano-N'-[1-(pyridin-2-yl)ethyl-idene]acetohydrazide.

In the title compound, C(10)H(10)N(4)O, the dihedral angle between the pyridine ring and the -C=O(CH(2))CN group is 24.08 (12)°. In the crystal, inversion dimers linked by pairs of N-H⋯N hydrogen bonds generate R(2) (2)(8) loops.

[Role of 5-HT(2A) receptor in increase in respiratory-related rhythmic discharge activity by nikethamide in neonatal rat transverse medullary slices].

To investigate the effects of nikethamide on the generation and modulation of rhythmic respiration of neonatal rats and the role of 5-HT(2A) receptor in this course, experiments were performed on the transverse medullary slices of neonatal rats (both sexes, 1-3 d) in vitro. The slices containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets were prepared in which the respiratory-related rhythmic discharge activity (RRDA) was recorded from the hypoglossal nerve rootlets by suction electrode. The possible role of nikethamide on RRDA was investigated by administration of an agonist of 5-HT(2A) receptor, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and an antagonist of 5-HT(2A) receptor, ketanserine, dissolved in modified Krebos solution (MKS). Thirty slices were randomly divided into five groups: Group 1: the slices were perfused with different concentrations of nikethamide (0.5, 1, 3, 5, 7, 10 µg/mL), and the most effective concentration was selected; Group 2: the slices were perfused with DOI (40 µmol/L); Group 3: the slices were perfused with ketanserine (40 µmol/L); Group 4: the slices were perfused with ketanserine + DOI; Group 5: the slices were perfused with nikethamide, then perfused with nikethamide + ketanserine after washout of nikethamide. Nikethamide increased RRDA in transverse medullary slices at 0.5-7 µg/mL, and 5 µg/mL was the most effective concentration. DOI increased RRDA with prolonged inspiratory time (TI), increased integral amplitude (IA), and shortened respiratory cycle (RC). Ketanserine decreased RRDA with shortened TI, decreased IA and prolonged RC. Ketanserine + DOI had no significant effects on RRDA. The effects of nikethamide on RC and IA were totally and partially reversed by additional application of ketanserine, but the effect of nikethamide on TI was not influenced by ketanserine. It is proposed that nikethamide increases RRDA partly via 5-HT(2A) receptors.

[Role of histamine H(1) and H(2) receptors in the modulation of respiratory rhythmical discharge in medulla oblongata slice preparation of neonatal rats].

The present study was carried out to determine the role of histamine H(1) and H(2) receptors in the generation of basic respiratory rhythm. Neonatal (aged 0-3 d) Sprague-Dawley rats of either sex were used. The medulla oblongata slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O(2) and 5% CO(2)), and ended in 3 min. Respiratory rhythmical discharge activity (RRDA) of the rootlets of hypoglossal nerve was recorded by suction electrode. Thirty medulla oblongata slice preparations were divided into 5 groups. In groups I, II and III, histamine (5 µmol/L), H(1) receptor specific antagonist pyrilamine (10 µmol/L) and H(2) receptor specific antagonist cimetidine (5 µmol/L) was added into the perfusion solution for 15 min separately. In group IV, after application of histamine for 15 min, additional pyrilamine was added into the perfusion for another 15 min. In group V, after application of histamine for 15 min, additional cimetidine was added into the perfusion for another 15 min. The discharges of the roots of hypoglossal nerve were recorded. Signals were amplified and band-pass filtered (100-3.3 kHz). Data were sampled (1-10 kHz) and stored in the computer via BL-420 biological signal processing system. Our results showed that histamine significantly decreased the respiratory cycle (RC) and expiratory time (TE), but changes of integral amplitude (IA) and inspiratory time (TI) were not statistically significant. Pyrilamine induced significant increases in RC and TE, but changes of TI and IA were not statistically significant. Cimetidine had no effects on RC, TE, TI and IA of RRDA. The effect of histamine on the respiratory rhythm was reversed by additional application of pyrilamine but not cimetidine. Taken together, with the results mentioned above, histamine H(1) receptors but not H(2) receptors may play an important role in the modulation of RRDA in the medulla oblongata slice preparation of neonatal rats.

Up-regulation of ICAM-1mRNA and IL-1ßmRNA in lung tissues of a rat model of COPD.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by airflow obstruction that is usually progressive and not fully reversible. It is accompanied by the abnormal inflammatory response of lung to toxic particles or gas. Studies indicate that chronic inflammatory injuries of airway, pulmonary parenchyma and pulmonary vessels are the characteristic changes of COPD. Adhesion of inflammatory cells is the important link of pulmonary infection. Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein involved in binding with mediated cells or with the extracellular matrix in the process called cell adhesion. IL-1ß is an important inflammatory mediator as well as the promoter and critical inducer of cytokine cascade reaction. In this study, the rat model of COPD was established by smoking + intratracheal instillation of LPS (the experimental group). PaO2 and PaCO2 were measured. ICAM-1mRNA and IL-1ßmRNA level in lung homogenate were detected by immunohistochemistry and RT-PCR and were compared with those of the rats treated by smoke exposure (the control group) and the healthy rats (the blank group) in order to investigate the effect of ICAM-1 and IL-1ß in lung injury of COPD. This study showed that the respiratory function of rats with COPD was decreased. PaO2 of rats in the experimental group, the control group and the blank group decreased successively, and the comparison between any two groups had significant difference. PaCO2 increased successively, and the comparison between any two groups had significant difference. Immunohistochemistry results showed that protein expression of ICAM-1 and IL-1ß in lung tissues of rats in the experimental group was higher than that in the control group and the blank group, and the comparison between any two groups had significant difference. RT-PCR results showed that ICAM-1mRNA and IL-1ßmRNA level of rats in the experimental group was higher than that in the control group and the blank group, and the comparison between any two groups had significant difference. This study indicated that the decreased respiratory function of rats with COPD was associated with the imbalance of inflammatory cascade and the up-regulation of ICAM-1mRNA and IL-1ßmRNA in lung tissues and cells caused inflammatory injury and decreased respiratory function.

Neurotoxicity of prenatal alcohol exposure on medullary pre-Bötzinger complex neurons in neonatal rats.

Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor (5-HT2AR) is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10% (v/v) throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2AR protein and mRNA levels in the pre-Bötzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2AR protein and mRNA levels.

[Effect of prenatal alcohol exposure on rhythmic respiratory discharge activity in medullary slices of neonatal rats].

OBJECTIVE: To investigate the effects of prenatal alcohol exposure on rhythmic respiratory discharge activity (RRDA) in the medullary slices of neonatal rats. METHODS: Ten pregnant female SD rats were exposed to 0, 4%, 6%, 8%, and 10% alcohol in drinking water from 1 week before till 3 days after delivery. The medullary slices of the neonatal rats containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb's solution to record RRDA from the hypoglossal nerve rootlets using suction electrodes. RESULTS: No significant difference was found in RRDA in 50 min among the neonatal rats with prenatal exposure to 0, 4%, 6%, and 8% alcohol, but the RRDA in 10% alcohol exposure group became irregular. Prenatal exposure to increased alcohol concentrations caused attenuated RRDA attenuated in the neonatal rats, shown by shortened inspiratory time (TI), decreased respiratory frequency (RF), and reduced integral amplitude (IA) as compared with those in the control group. CONCLUSION: Prenatal alcohol exposure inhibits RRDA in medullary slices of neonatal rats, which might be a mechanism by which maternal alcohol exposure causes suppressed offspring respiratory functions.

Protocatechuic acid improves cognitive deficits and attenuates amyloid deposits, inflammatory response in aged AßPP/PS1 double transgenic mice.

Protocatechuic acid (PCA), a phenolic compound of Radix Salviae Miltiorrhizae (RSM), has been found to have a protective effect on improving cognitive deficits in STZ-induced AD rats. The present study aimed to evaluate the potential protection activity of PCA on improving cognitive deficits and attenuating Aß deposition and inflammatory responses in aged AßPP/PS1 double transgenic AD-model mice. The results of Morris water maze test showed that PCA (100mg/kg) significantly prolonged the mean latency time and the path length of AßPP/PS1 mice. PCA could significantly reduce the number of Aß positive expressions in the hippocampus and cerebral cortex of AßPP/PS1 mice by immunocytochemical assay with Congo red staining and decrease remarkably APP expression level by Western blot analysis (P<0.01). The results from ELISA and Western blot analysis showed that the levels of inflammatory cytokines including TNF-α, IL-1ß, IL-6 and IL-8 decreased remarkably by the treatment with PCA (P<0.01). Further, there was a substantial increase of brain derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex of AßPP/PS1 mice treated with PCA (P<0.01). The present study provided confirmatory evidence that PCA significantly decreased Aß deposits, APP and inflammatory response, whereas increased learning and memory ability, as well as enhanced BDNF level. Our findings indicated that PCA is an effective neuroprotective agent for AD therapy. It might be associated with the attenuation on Aß deposits and inflammation responses involved in the process.

[Histamine H1 receptors modulate the discharge activities of inspiratory neurons in the medial region of neonatal rat nucleus retrofacialis ex vivo].

OBJECTIVE: To investigate the role of histamine H1 receptors in modulating the discharge activities of the inspiratory neurons in the nucleus retrofacialis of neonatal rats. METHODS: Brainstem slices were obtained from neonatal rats containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve (XII nerve) rootlets retained. The rhythmic discharges of the inspiratory neurons (I neurons) and activities of the XII nerve rootlets were simultaneously recorded using microelectrodes and suction electrodes, respectively. The role of H1 receptors in modulation of the discharge activities of the inspiratory neurons was investigated using the H1 receptor agonist histamine and its specific antagonist pyrilamine dissolved in modified Kreb's solution for slice perfusion. RESULTS: Histamine shortened the respiratory cycle (RC) and expiratory time (TE) of the neurons in the brain slices, and pyrilamine produced the opposite effects. Neither histamine nor pyrilamine affected the inspiratory time (TI), integral amplitude (IA) or the peak discharge frequency (PF) of the I neurons. CONCLUSION: H1 receptors play an excitatory role in the modulation of the discharge activities of the inspiratory neurons in neonatal rat brainstem slices.

[Glycine is involved in the modulation of respiratory rhythmical discharge activity in neonatal rat medullary brain slices].

OBJECTIVE: To determine the role of glycine (Gly) in the generation and modulation of basic respiratory rhythm. METHODS: Neonatal (0-3 days) SD rats of either sex were used in this study. The medulla oblongata brain slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared, and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O(2) and 5% CO(2)) within 3 min. The rhythmical respiratory discharge activity (RRDA) of the hypoglossal nerve rootlets was recorded using suction electrode. Eighteen medulla oblongata slice preparations were divided into 3 groups and treated for 20 min with Gly receptor specific agonist Gly (10 micromol/L), Gly receptor antagonist strychnine (STR, 1 micromol/L), or Gly+STR after a 20 min Gly application. The changes in RRDA of the hypoglossal nerve rootlets were observed. RESULTS: Gly significantly decreased the inspiratory time and integral amplitude (IA), but the changes of respiratory cycle (RC) and expiratory time (TE) were not statistically significant. STR induced a decrease in expiratory time and respiratory cycle without significantly affecting the inspiratory time or integral amplitud. The effect of Gly on the respiratory rhythm was partially reversed by additional application of STR. CONCLUSION: Gly may play an important role in the modulation of RRDA in the medulla oblongata slice of neonatal rats.

[GABA A receptor participates in respiratory enhancement induced by nikethamide in neonatal rats].

OBJECTIVE: To investigate the role of GABA A receptor in nikethamide-induced respiratory enhancement in the medullary slices of neonatal rats. METHODS: Ex vivo medullary slices of neonatal rats (1 to 3 days old) containing the medial region of the nucleus retrofacialis with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb's solution to record respiration-related rhythmic discharge activity (RRDA) from the hypoglossal nerve rootlets using suction electrodes. Thirty RRDA-positive slices were randomized into 5 equal groups and perfused with nikethamide (at concentrations of 0.5, 1, 3, 5, 7, and 10 microg/ml with the optimal nikethamide concentration determined), GABA (at 10, 20, 40, and 60 micromol/ to determine the optimal concentration), 10 micromol/ bicuculline, 10 micromol/ bicuculline plus 40 micromol/L GABA, and 5 microg/ml nikethamide followed by 5 microg/ml nikethamide plus 10 micromol/ bicuculline after wash out, respectively. RESULTS: Nikethamide increased RRDA at the concentrations of 0.5-7 microg/ml, and 5 microg/ml nikethamide showed the most distinct effect on the inspiratory time (TI), integral amplitude (IA), and respiratory cycle (RC). GABA at 40 micromol/ showed the most effective inhibition of RRDA in terms of TI, IA, and RC. Bicuculline at 10 micromol/ could increase the IA, TI and RC, but the combination of 10 micromol/ bicuculline and 40 micromol/ GABA had no significant effects on RRDA. Compared with nikethamide used alone, nikethamide plus bicuculline significantly increased TI and IA without affecting RC. CONCLUSION: Nikethamide can enhance RRDA of the hypoglossal nerve rootlets in the medullary slices of neonatal rats, and the effect can be partially mediated by the GABA A receptor.