High-Sensitivity and Wide-Range Flexible Ionic Piezocapacitive Pressure Sensors with Porous Hemisphere Array Electrodes.

The development of high-performance flexible pressure sensors with porous hierarchical microstructures is limited by the complex and time-consuming preparation processes of porous hierarchical microstructures. In this study, a simple modified heat curing process was first proposed to achieve one-step preparation of porous hemispherical microstructures on a polydimethylsiloxane (PDMS) substrate. In this process, a laser-prepared template was used to form surface microstructures on PDMS film. Meanwhile, the thermal decomposition of glucose monohydrate additive during heat curing of PDMS led to the formation of porous structures within PDMS film. Further, based on the obtained PDMS/CNTs electrodes with porous hemisphere array and ionic polymer dielectric layers, high-performance ionic piezocapacitive sensors were realized. Under the synergistic effect of the low-stiffness porous hemisphere microstructure and the electric double layer of the ionic polymer film, the sensor based on an ionic polymer film with a 1:0.75 ratio of P(VDF-HFP):[EMIM][TFSI] not only achieves a sensitivity of up to 106.27 kPa-1 below 3 kPa, but also has a wide measurement range of over 400 kPa, which has obvious advantages in existing flexible piezocapacitive sensors. The rapid response time of 110 s and the good stability of 2300 cycles of the sensor further elucidate its practicality. The application of the sensor in pulse monitoring, speech recognition, and detection of multiple dynamic loads verifies its excellent sensing performance. In short, the proposed heat curing process can simultaneously form porous structures and surface microstructures on PDMS films, greatly simplifying the preparation process of porous hierarchical microstructures and providing a simple and feasible way to obtain high-performance flexible pressure sensors.

Blockade of Indoleamine 2,3-Dioxygenase attenuates lipopolysaccharide-induced kidney injury by inhibiting TLR4/NF-κB signaling.

Blockade of indoleamine 2,3-dioxygenase (IDO) has been shown to alleviate lipopolysaccharide (LPS)-induced endotoxic shock and reduce sepsis mortality, but its effect on LPS-induced kidney damage has not been reported. Herein, we established a mouse kidney injury model by intraperitoneal injection of 10 mg/kg LPS and established an in vitro renal tubular epithelial cell injury model by stimulating TCMK-1 cells with 10 mg/L LPS. We found that pretreatment with 1-methyl tryptophan (1-MT), an IDO inhibitor, significantly improved LPS-induced mouse survival, and IDO knockout (KO) mice also had higher survival rates after LPS exposure than wild-type mice. At the same time, IDO KO or pretreatment with 1-MT not only reduced serum creatinine, blood urea nitrogen, renal tubular injury pathological score, but also inflammatory factors and oxidative stress status in serum or kidney of LPS-exposed mice. In vitro, blockade of IDO with 1-MT significantly inhibited LPS-induced apoptosis, inflammation and oxidative stress in TCMK-1 cells. In addition, blockade of IDO significantly inhibited LPS-activated TLR4/NF-κB signaling pathway in kidney of mice or in TCMK-1 cells. In conclusion, our results suggested that blockade of IDO attenuated kidney inflammation, apoptosis and oxidative stress to protect against LPS-induced septic kidney injury via inhibiting the TLR4/NF-κB signaling pathway.

Alteration of ghrelin/obestatin ratio in adolescence with polycystic ovarian syndrome.

Ghrelin, an endoggenous for the growth hormone secretagogue receptor, has been shown to participate in the regulation of energy homeostasis and pituitary hormone secretion. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. Ghrelin and obestatin are altered in polycystic ovary syndrome (PCOS), which is characterized by insulin resistance and pituitary hormone secretion disorder. The aim of this study was to evaluate ghrelin/obestatin imbalance in relation to insulin resistance and pituitary hormone in adolescence with PCOS. This restrospective case-control study included 33 adolescence with PCOS and 38 control adolescence. Ghrelin and obestatin concentrations in serum were determined by RIA, and the serum fasting glucose and Insulin were determined by the glucose oxidase color method and INS-EASIA. The serum LH and FSH were measured by highly specific hemiluminescence immunoassays. We found that the serum ghrelin levels and ghrelin/obestatin ratio were significant lower in PCOS group than in control group, and the serum obestatin levels were significant higher in PCOS group than in control group. The ghrelin/obestatin ratios were negatively correlation with LH/FSH ratio and insulin resistant index in PCOS group. The findings of this study suggest that ghrelin/obestatin imbalance may play a role in pathogenesis of adolescent PCOS.

Up-Regulation of miR-204 Enhances Anoikis Sensitivity in Epithelial Ovarian Cancer Cell Line Via Brain-Derived Neurotrophic Factor Pathway In Vitro.

OBJECTIVE: Genomic loci encoding miR-204, which was predicted to target brain-derived neurotrophic factor (BDNF), were frequently lost in multiple cancer, including epithelial ovarian cancer (EOC). In this study, we aimed to find out the influence of miR-204 expression level on EOC cell anoikis sensitivity and to explore possible mechanisms of this process. METHODS: First, we screened EOC cells, which maintain anoikis resistance forming an anoikis pattern. miR-204 expression level and apoptosis were measured, respectively, by quantitative reverse transcriptase polymerase chain reaction and Annexin-V-R-PE/7-amino-actinomycin assay. Then we restored the expression level of miR-204 by transfection with pre-miR-204. miR-204 expression level and apoptosis were measured as before; cell invasion and migration ability were detected by transwell invasion assay and wound-healing assay. The messenger RNA level of BDNF was also detected by quantitative reverse transcriptase polymerase chain reaction; Western blot analysis was performed to assess pAKT expression. RESULTS: Expression of miR-204 is significantly down-regulated in an anoikis pattern. Restored expression level of miR-204 enables cells to acquire more sensitivity to anoikis and decrease invasive and metastatic behavior, and also results in BDNF down-expression and inhibits activation of mitochondria-dependent pathway through the PI3K/AKT signaling pathway leading to cancer cell anoikis in EOC cells. CONCLUSIONS: miR-204 up-regulation may be linked directly to the sensitivity of EOC cell anoikis by contributing to BDNF down-regulation. Our findings provide a novel mechanism for manipulating miR-204 levels therapeutically to restore anoikis sensitivity.

Stromal cell-derived factor-1 (SDF-1) enhances cells invasion by αvß6 integrin-mediated signaling in ovarian cancer.

Ovarian carcinoma is a common gynecological malignancy and a great threat to health as a result of metastasis. The chemokine stromal-derived factor (SDF-1) plays multiple roles in tumor pathogenesis. However, the precise molecular mechanism underlying SDF-1-induced ovarian cancer cell invasion is still undefined. αvß6 integrin is an important factor in tumor progression. Therefore, we speculate that SDF-1-enhanced ovarian cancer cell invasion is related to αvß6 integrin-mediated signaling. After culturing with SDF-1, an obvious time- and dose-dependent increase in αvß6 integrin was demonstrated. Furthermore, CXC receptor 4 (CXCR4) was responsible for SDF-1-induced αvß6 integrin expression. Simultaneously, SDF-1 was found to dramatically enhance extracellular matrix degradation via urokinase-type plasminogen activator (uPA) expression and cell invasion by αvß6 integrin expression; these reinforce failed to be increased when pretreatment was performed with the CXCR4 inhibitor AMD3100 or anti-αvß6 integrin antibody, respectively. In addition, αvß6 integrin induced the phosphorylation of p38 MAPK and PI3 K/Akt, contributing to the up-regulation of uPA, as treatment with the specific inhibitor for p38 mitogen-activated protein kinases (MAPK) (SB203580) or phosphatidylinositol 3-kinase (PI3 K)/Akt (LY294002) strikingly abrogated uPA expression. Taken together, these results demonstrated that SDF-1 enhanced ovarian cancer cell invasion through αvß6 integrin-mediated uPA expression via the p38 MAPK and PI3 K/Akt pathway. Consequently, our findings will provide a new explanation about how SDF-1 aggravates the pathogenesis of ovarian cancer.

RNA interference targeting CD147 inhibits the invasion of human cervical squamous carcinoma cells by downregulating MMP-9.

Cervical squamous carcinoma is a highly invasive tumour that has a great capacity to metastasise. Extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin superfamily, is a widely distributed cell surface glycoprotein. It is highly expressed on malignant tumour cell surfaces, including human cervical squamous carcinoma. It also plays a critical role in the invasive and metastatic activity of malignant cells by stimulating the expression of matrix metalloproteinases (MMPs). The anti-invasive effect of small interfering RNA (siRNA) against CD147 on human cervical squamous carcinoma cells and its possible pathways has been investigated. The downregulation of CD147 by transfection with siRNA resulted in MMP-9 expression and decreased activity in the cervical squamous carcinoma cell line SiHa. In vitro analysis showed that the invasive capacity of SiHa cells decreased. Thus CD147 inhibition and subsequent MMP-9 deletion may have anti-tumour effects by inhibiting the invasiveness of human cervical squamous carcinoma cells.

[Di-(2-ethylhexyl) phthalate activates the apoptosis Caspase pathway in rat Leydig cells in vitro].

OBJECTIVE: To investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on the expressions of Caspase-3 and Caspase-9 genes in rat Leydig cells and the apoptosis of the cells in vitro. METHODS: Leydig cells were isolated from male SD rats, primarily cultured and treated with DEHP at a low (10 nmol/L), a medium (50 nmol/L) and a high dose (100 nmol/L) for 24 hours. Then the mRNA expressions of Caspase-3 and Caspase-9 genes in the Leydig cells were detected by real time PCR, their protein expressions determined by Western blot, and the apoptosis of the Leydig cells measured by flow cytometry. RESULTS: Compared with the DMSO control group, the low-, medium- and high-dose DEHP groups showed significantly upregulated expressions of Caspase-3 mRNA (1.69 +/- 0.38 vs 3.82 +/- 0.39, 6.91 +/- 0.40 and 15.47 +/- 0.40, P < 0.05), Caspase-3 protein (0.18 +/- 0.0.09 vs 0.32 +/- 0.10, 0.61 +/- 0.08 and 0.89 +/- 0.09, P < 0.05), Caspase-9 mRNA (2.24 +/- 0.41 vs 5.16 +/- 0.43, 9.61 +/- 0.45 and 19.22 +/- 0.43, P < 0.05) and Caspase-9 protein (0.26 +/- 0.07 vs 0.40 +/- 0.08, 0.68 +/- 0.09 and 0.96 +/- 0.08, P < 0.05), as well as increased apoptosis rate of Leydig cells (4.36 +/- 1.11 vs 7.52 +/- 1.09, 12.72 +/- 1.10 and 24.59 +/- 1.11, P < 0.05), all in a dose-dependent manner. CONCLUSION: DEHP can induce the apoptosis of rat Leydig cells by activating the apoptosis Caspase pathway, and consequently affect the function of Leydig cells.

One-Step Laser Direct-Printing Process of a Hybrid Microstructure for Highly Sensitive Flexible Piezocapacitive Sensors.

Microstructures can effectively improve the sensing performance of flexible piezocapacitive sensors. Simple, low-cost fabrication methods for microstructures are key to facilitating the practical application of piezocapacitive sensors. Herein, based on the laser thermal effect and the thermal decomposition of glucose, a rapid, simple, and low-cost laser direct-printing process is proposed for the preparation of a polydimethylsiloxane (PDMS)-based electrode with a hybrid microstructure. Combining the PDMS-based electrode with an ionic gel film, highly sensitive piezocapacitive sensors with different hybrid microstructures are realized. Due to the good mechanical properties brought about by the hybrid microstructure and the double electric layer induced by the ionic gel film, the sensor with a porous X-type microstructure exhibits an ultrahigh sensitivity of 92.87 kPa-1 in the pressure range of 0-1000 Pa, a wide measurement range of 100 kPa, excellent stability (>3000 cycles), fast response time (100 ms) and recovery time (101 ms), and good reversibility. Furthermore, the sensor is used to monitor human physiological signals such as throat vibration, pulse, and facial muscle movement, demonstrating the application potential of the sensor in human health monitoring. Most importantly, the laser direct-printing process provides a new strategy for the one-step preparation of hybrid microstructures on thermal curing polymers.

Silencing of long non-coding RNA ZFAS1 alleviates LPS-induced acute lung injury by mediating the miR-96-5p/OXSR1 axis in sepsis.

BACKGROUND: Extensive studies have revealed that long non-coding RNAs (lncRNAs) are associated with sepsis-induced acute lung injury (ALI). This study focused on the function and potential mechanisms of lncRNA zinc finger antisense 1 (ZFAS1) in a cell model of sepsis-induced ALI. METHODS: To induce sepsis-induced ALI in vitro and in vivo, mice were subjected to cecal ligation and puncture (CLP) operation, and human small airway epithelial cells (HSAECs) were stimulated with lipopolysaccharide (LPS) (10 µg/mL). Relative expression of oxidative stress-responsive 1 (OXSR1), lncRNA ZFAS1, and microRNA (miR)-96-5p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Relative protein expression of Bax, Bcl-2, and OXSR1 was determined by western blotting. Moreover, enzyme-linked immunosorbent assay was used to measure the levels of IL-6, IL-1ß, and TNF-α. A dual-luciferase reporter assay was conducted to test the targeting interplay between ZFAS1/OXSR1 and miR-96-5p. RESULTS: Up-regulation of lncRNA ZFAS1 and OXSR1 and down-regulation of miR-96-5p was observed in lung tissues of CLP-induced mice and LPS-treated HSAECs. Decreased ZFAS1 expression or increased miR-96-5p expression repressed inflammation and apoptosis and promoted cell viability in LPS-treated HSAECs. The lncRNA ZFAS1 competitively binds to miR-96-5p and inversely modulates miR-96-5p expression. MiR-96-5p directly targets OXSR1 and inversely regulates OXSR1 expression. In addition, the protective effects of ZFAS1 knockdown on LPS-induced HSAECs were reversed by miR-96-5p inhibition or OXSR1 overexpression. CONCLUSIONS: Down-regulation of lncRNA ZFAS1 attenuated LPS-induced ALI in HSAECs by regulating the miR-96-5p/OXSR1 axis.

Organization model, vertical integration, and farmers' income growth: Empirical evidence from large-scale farmers in Lin'an, China.

Since China's reform and opening-up in 1978, the income of rural residents has increased when compared with that of urban residents. However, the income growth rate of farmers is relatively low, and the income gap between urban and rural areas is widening. Using a sample of 1,325 large-scale farming households in Lin'an, this study constructs a theoretical path for how the level of vertical integration and an organization model affect farmers' income levels and empirically tests the path using a mediation effect analysis model. The results indicate that organization models and vertical integration are important factors that affect farmers' income levels. The total income and agricultural operation income of farmers who participate in agricultural operation organizations are greater than that of farmers who do not participate in an operation organization. In addition, the total income and agricultural operation income of farmers who produce and process and those who produce, process, and sell are higher than those of farmers who only produce. A farmers' organization model has both a direct and an indirect positive influence on their income level, with the indirect positive influence coming through the mediating variable of vertical integration. The application of the organizational model can promote the growth of rural households' total family income and agricultural income by 13.48% and 14.48% respectively, consisting of direct increases of 9.67% and 10.19%, and indirect increases of 3.81% and 4.29% through vertical integration. The results also show that access to credit, agricultural technology training, and the farmer's education level have significant positive impacts on farming income levels. The findings suggest ways to increase farmers' income by perfecting agricultural management organization systems, promoting agricultural industrialization, strengthening rural financial support, improving agricultural technical training for farmers, and increasing their level of education.

Effects of Survivin on cell proliferation and apoptosis in MG-63 cells in vitro.

Osteosarcoma is the most frequent primary malignant tumor of the skeleton and occurs mainly in children and adolescent. The prognosis of osteosarcoma is very poor due to its aggressive and no effective treatment. This study is the first to investigate the anti-cancer effects of antisense pEGFP-C1-Survivin on human osteosarcoma cells. It was shown in our results that Survivin blockaded could significantly induce apoptosis and inhibit the invasive of osteosarcoma cells line MG-63. The effects were probably produced by the decreased expression of Survivin induced by antisense pEGFP-C1-Survivin which was examined by RT-PCR and western blotting. All these suggested that Survivin should be very important in the development of osteosarcoma and Survivin blockaded by using antisense pEGFP-C1-Survivin could markedly inhibit the proliferation and invasion of osteosarcoma cells line MG-63, partially reversed their malignant phenotype. Targeting Survivin might be a promising option in the treatment of osteosarcoma.

Maternal serum ratio of ghrelin to obestatin decreased in preeclampsia.

OBJECTIVE: Ghrelin, an endogenous for the growth hormone secretagogue receptor, has been shown to participate in blood pressure regulation. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. We hypothesized that ghrelin/obestatin imbalance played a role in the pathogenesis. This study was designed to determine the alterations of ghrelin and obestatin concentrations and ghrelin/obestatin ratio in maternal serum in preeclampsia. METHOD: This retrospective case-control study included 31 preeclampsia and 31 gestational week-matched normal pregnancies. Ghrelin and obestatin concentrations in maternal serum were determined by radioimmunoassay, and the ghrelin/obestatin ratio was calculated. RESULTS: The ghrelin concentration and ghrelin/obestatin ratio in maternal serum were significantly lower in preeclampsia than in normal pregnancies (214.34±14.27pg/mL vs 251.49±16.15pg/mL, P=0.041, 1.07±0.09 vs 0.82±0.08, P=0.023). The obestatin concentration in maternal serum was significantly higher in preeclampsia than in normal pregnancies (276.35±15.38pg/mL vs 223.53±18.61pg/mL, P=0.019). The systolic blood pressure in preeclampsia was negatively correlated with ghrelin concentration and ghrelin/obestatin ratio (r=-0.549, P=0.003; r=-0.491, P=0.004) and was positively correlated with obestatin concentrations in preeclampsia (r=0.388, P=0.013). CONCLUSIONS: The findings of this study suggested disturbance of ghrelin and obestatin in maternal serum in preeclampsia, and ghrelin/obestatin imbalance might play a role in the pathogenesis of preeclampsia.

AZD1480 can inhibit the biological behavior of ovarian cancer SKOV3 cells in vitro.

OBJECTIVE: To study the mechanism of effects of AZD1480 on the SKOV3 ovarian cancer cell line. METHODS: The MTT method was used to assess cellular proliferation, flow cytometry for cellular apoptosis, the scratch test to determine migration, transwell chamber assays to detect cellular invasion, plate clone experiments to detect the clone forming ability and Western blotting to determine p-STAT3 protein levels. RESULTS: The proliferation rate, migration ability, invasiveness and the clone forming ability of SKOV3 cells were reduced after treatment with AZD1480, while apoptosis rate and chemotherapeutic susceptibility were increased. After treatment with AZD1480 plus cisplatin, the apoptosis rate increased significantly while the expression level of p-STAT3 protein was decreased. CONCLUSION: AZD1480 can inhibit the proliferation, invasion, metastasis and clone formation of SKOV3 cells, induce cellulsar apoptosis, increase the chemotherapeutic sensitivity and reduce the expression level of p-STAT3 protein.

Expression profile of mammalian microRNAs in endometrioid adenocarcinoma.

MicroRNAs (miRNAs) are small noncoding RNAs of 19-24 nucleotides in length and involved in gene expression regulation. They are associated with cell proliferation, differentiation, apoptosis, and carcinogenesis. The specific expression profiles of miRNAs have been found in many human cancers, but there are few studies on endometrioid adenocarcinoma. We found the miRNA expression profile in 10 pairs of endometrioid adenocarcinoma and adjacent nontumorous endometrium using human miRNA microarray. Seventeen miRNAs exhibited higher expression and six miRNAs exhibited lower expression in endometrioid adenocarcinoma samples than those in the nontumorous samples in the microarray. Of those, the miR-205, miR-449, and miR-429 were greatly enriched; in contrast the miR-204, miR-99b, and miR-193b were greatly downregulated in adenocarcinoma tissues. The expressions of these six miRNAs were validated using real time reverse transcription-PCR. This information may provide the candidate miRNA genome for further confirming the role of miRNAs in carcinogenesis of endometrioid adenocarcinoma and potentially serving as a diagnostic or therapeutic tool in endometrioid adenocarcinoma.

[Construction of RNA recombinant vector expressing STAT3 short hairpin and its effects on proliferation and apoptosis of SiHa cells].

AIM: To investigate the effects of eukaryotic vector expressing short hairpin RNA (shRNA) of signal transducers and activators of transcription 3 (STAT3) on the proliferation and apoptosis of SiHa cells. METHODS: shRNA templates were designed based on STAT3 gene sequence and cloned into pSilencer2.1-U6-neo vector. The resultant plasmid was transfected into SiHa cells with Lipofectamine 2000. The STAT3 protein and mRNA were detected by Western blot and RT-PCR, respectively. The cellular growth activity was assayed by MTT and the apoptosis was tested by flow cytometry. RESULTS: The plasmid pSilencer2.1-U6-neo-STAT3 was successfully constructed and transfected into SiHa cells. The expression of STAT3 in SiHa cells decreased, the cellular growth activity decreased, and the cell apoptosis increased. CONCLUSION: The siRNA expressing plasmid pSilencer2.1-U6-neo-STAT3 can inhibit cellular proliferation and induce the apoptosis of cervical cancer cells by suppressing the expression of STAT3.

[The differential expression of hypoxia-inducible factor-1alpha in placenta tissues from pregnancy induced hypertension and normal pregnancy].

AIM: To explore the differential expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in placenta tissues from pregnancy induced hypertension and normal pregnancy. METHODS: The expression of HIF-1alpha protein and mRNA was detected by Western blot and real-time PCR, respectively. RESULTS: As compared with the expression levels of HIF-1alpha protein and mRNA in placenta tissues from normal pregnancy, those from pregnancy induced hypertension increased notably (P<0.05). CONCLUSION: The high expression of HIF-1alpha in the placenta tissues pregnancy induced may relate with pathogenesis and pathophysiological process of hypertension.