Flexible fabric gas sensors based on reduced graphene-polyaniline nanocomposite for highly sensitive NH3detection at room temperature.

A flexible fabric gas sensor for the detection of sub-ppm-level NH3is reported in this paper. The reduced graphene oxide (rGO)-polyaniline (PANI) nanocomposite was successfully coated on cotton thread via anin situpolymerization technique. The morphology, microstructure and composition were analyzed by field-emission scanning electron microscope, x-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy. Furthermore, we have studied the responses of the rGO-PANI nanocomposite-based flexible sensors for the detection of NH3varying from 1-100 ppm, operated at 22 °C. At the optimized concentration of rGO, the response of these sensors increased by 4-5 times in comparison with the pristine rGO and PANI. These flexible sensors exhibited fast response, remarkable long-term stability, good selectivity and a low detection limit. The sensing mechanism for the high sensing performance has been thoroughly discussed and it is mainly due to the distinctive 1D fiber structure, the formation of a p-p heterojunction between the rGO nanosheets and PANI. The rGO-PANI composite-based fabric sensor with low power consumption is a potential flexible electronic device for the detection of NH3.

FOXD3 may be a new cellular target biomarker as a hypermethylation gene in human ovarian cancer.

BACKGROUND: FOXD3 is aberrantly regulated in several tumors, but its underlying mechanisms in ovarian cancer (OC) remains largely unknown. The present study aimed to explore the role and associated mechanisms of FOXD3 in OC. METHODS: Microarray data from GEO was used to analyze differential CpG sites and differentially methylated regions (DMR) in tumor tissues and Illumina 450 genome-wide methylation data was employed. The FOXD3 expression level was determined through qRT-PCR and western blot analysis. Wound healing test, colony formation and flow cytometry assay were utilized to analyze cell migration, proliferation abilities, cell cycle and cell apoptosis, respectively. Finally, the effect of FOXD3 on tumor growth was investigated through in vivo xenograft experiments. RESULTS: GEO data analysis showed that FOXD3 was hypermethylated in OC tissues. Also, qRT-PCR revealed that FOXD3 was low expressed and methylation-specific PCR (MSP) confirmed that the methylation level of FOXD3 was hypermethylated. Combined treatment of 5-aza-2'-deoxycytidine (5-Aza-dC) could synergistically restored FOXD3 expression. Finally, in vitro and in vivo experiments showed that demethylated FOXD3 decreased cell proliferation and migration abilities, and increased the cell apoptosis. In vivo experiment detected that demethylated FOXD3 restrained tumor growth. CONCLUSIONS: FOXD3 could act as a tumor suppressor to inhibit cell proliferation, migration and promote cell apoptosis in OC cells.

Transcriptome sequencing analysis reveals miR-30c-5p promotes ferroptosis in cervical cancer and inhibits growth and metastasis of cervical cancer xenografts by targeting the METTL3/KRAS axis.

Cervical cancer is the most common malignant tumor in the female reproductive system worldwide, and its molecular mechanisms remain complex and poorly understood. Various techniques, including transcriptome sequencing, RT-qPCR, ELISA, immunofluorescence, Western blot, CCK-8 assay, Transwell assay, and xenograft models, were employed to investigate gene/miRNA expression, cellular proliferation, migration, and the interactions between miR-30c-5p, METTL3, and KRAS. Our transcriptome sequencing results demonstrated a significant downregulation of miR-30c-5p in cervical cancer cells. Further investigations using RNA pull-down, dual-luciferase reporter assay, Me-RIP, and PAR-CLIP confirmed METTL3 as one of the downstream targets of miR-30c-5p, while KRAS was identified as an iron-death suppressor gene susceptible to m6A modification. Notably, our Me-RIP analysis demonstrated the involvement of METTL3 in m6A modification of KRAS. In vitro experiments revealed that miR-30c-5p facilitated ferroptosis in cervical cancer cells by inhibiting the METTL3/KRAS axis, thus suppressing proliferation and migration. Additionally, in vivo studies demonstrated that miR-30c-5p repressed the growth and metastasis of cervical cancer xenografts through the inhibition of the METTL3/KRAS axis. Overall, this study highlights the critical role of miR-30c-5p in modulating cervical cancer progression by targeting the METTL3/KRAS axis, providing new insights into the molecular mechanisms underlying cervical cancer growth and metastasis.

Atherosclerosis: From the Disruption of Mitochondrial Membrane Potential to the Potential Interventional Strategies.

Atherosclerosis (AS) is the major factor of cardiovascular disease (CVD) and is characterized by a progressive and chronic inflammatory process in the arterial wall. Recent studies have shown that disruption of the mitochondrial membrane potential (deltapsi (m)) directly affects the electron transport chain (ETC), which in turn leads to oxidative stress, and furthermore, its alteration leads to apoptosis and activation of the NLRP3 inflammasome, thereby promoting the development of AS. Here, this review describes how deltapsi (m) contributes to the development of AS by mediating oxidative stress, apoptosis, and NLRP3 inflammasome activation, and potential AS intervention strategies by targeting oxidative stress, apoptosis, and NLRP3 inflammasome activation induced by deltapsi (m).

Effect of Exosomal lncRNA MALAT1/miR-370-3p/STAT3 Positive Feedback Loop on PI3K/Akt Pathway Mediating Cisplatin Resistance in Cervical Cancer Cells.

Background: Exosomes can encapsulate lncRNA to mediate intercellular communication in cancer progression. Our study devoted to research the effect that long noncoding RNA Metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) influence on cervical cancer (CC). Methods: MALAT1 and miR-370-3p levels in CC was assessed using qRT-PCR. CCK-8 assay and flow cytometry were devoted to confirm the influence on MALAT1 influencing the proliferation in cisplatin-resistant CC cells. Futher more, MALAT1, combined with miR-370-3p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: In CC tissues, MALAT1 turned into substantially expressed, cisplatin-resistant cell lines, as well as exosomes. Cell proliferation was restrained and cisplatin-induced apoptosis was promoted by way of Knockout MALAT1. And promoted the miR-370-3p level, MALAT1 targeted miR-370-3p. Promoting effect of MALAT1 on cisplatin resistance of CC was partially reversed through miR-370-3p. In addition, STAT3 may induce up-regulation of MALAT1 expression in cisplatin-resistant CC cells. It was further confirmed that the effect of MALAT1 on cisplatin-resistant CC cells was achieved by activating PI3K/Akt pathway. Conclusion: The positive feedback loop of exosomal MALAT1/miR-370-3p/STAT3 mediates the cisplatin resistance of cervical cancer cells affecting PI3K/Akt pathway. Exosomal MALAT1 may become a promising therapeutic target for treating cervical cancer.

FOXD3 confers chemo-sensitivity in ovarian cancer through a miR-335/DAAM1/myosin II axis-dependent mechanism.

BACKGROUND: Chemotherapy is among the most common treatment methods for ovarian cancer (OC). However, chemoresistance limits the effectiveness of chemotherapy and leads to treatment failure. We herein investigate the biological effect of forkhead box D3 (FOXD3) in the chemoresistance of OC cells. METHODS: Expression of FOXD3, miR-335 and disheveled-associated activator of morphogenesis 1 (DAAM1) was detected in OC cells and tissues. The regulatory network of FOXD3/miR-335/DAAM1 was validated by dual-luciferase reporter and ChIP assays in vitro. After ectopic expression and depletion experiments in carboplatin/paclitaxel (CP)-resistant (A2780CP) or sensitive (A2780S) OC cells, cell viability, colony formation and apoptosis were tested by CCK-8 assay, colony formation assay and flow cytometry respectively. Effects of FOXD3 on the chemoresistance of OC cells in vivo were evaluated in OC xenografts in nude mice. RESULTS: Overexpression of FOXD3 impaired the proliferation and chemoresistance of OC cells, which was related to the promotion of the miR-335 expression. Functionally, DAAM1 was a putative target of miR-335. Silencing of DAAM1 was responsible for the inhibition of myosin II activation, consequently leading to suppressed OC cell proliferation and chemoresistance. In vivo results further showed that FOXD3 weakened the chemoresistance of OC cells to CP. CONCLUSION: Taken together, we unveil a novel FOXD3/miR-335/DAAM1/myosin II axis that regulates the chemoresistance of OC both in vitro and in vivo.

Effect of MiR-375 Regulates YAP1 on the Invasion, Apoptosis, and Epithelial-Mesenchymal Transition of Cervical Cancer HeLa Cells.

Yes-associated protein 1 (YAP1) is an important signaling pathway activator molecule. Studies have shown that it is involved in the occurrence of malignant tumors. This study identified a microRNA (miR/miRNA) targeting the 3' untranslated region (3″ utr) of the YAP1 gene and evaluated its biological impact on human cervical cancer cells and related molecular mechanisms. qPCR and western blotting were used to detect the levels of miR-375 and YAP1 in HeLa cells. TargetScan software was used to identify the binding sites of YAP1 and miR-375. The MTT method was used to determine the viability of HeLa cells transfected with miR-375 mimic and YAP1 interference vector, the Transwell chamber experiment was used to detect the invasion of HeLa cells after transfection, the apoptosis of HeLa cells after transfection was detected by flow cytometry, and the western blotting was used to detect the epithelial mesenchymal transition (EMT) of HeLa cells after transfection. The expression of miR-375 in HeLa cells was significantly lower than that of normal control cervical cells, and the expression of YAP1 in HeLa cells was significantly higher than that of normal control cervical cells. TargetScan analysis showed that miR-375 was bound to the 3' UTR of YAP1. qPCR and western blot analysis showed that transfection of miR-375 mimics inhibited YAP1 expression in HeLa cells. Transfection of miR-375 mimic and YAP1 interference vector inhibited HeLa cell invasion and EMT and promoted HeLa cell apoptosis. These findings indicate that miR-375 inhibits the malignant development of human cervical cancer cells by regulating the expression of YAP1.

Silencing of hsa_circ_0009035 Suppresses Cervical Cancer Progression and Enhances Radiosensitivity through MicroRNA 889-3p-Dependent Regulation of HOXB7.

Circular RNAs (circRNAs), a novel type of endogenous noncoding RNAs, have been identified as critical regulators in human carcinogenesis. Here, we investigated the precise actions of hsa_circ_0009035 in the progression and radioresistance of cervical cancer (CC). The levels of hsa_circ_0009035, microRNA 889-3p (miR-889-3p), and homeobox B7 (HOXB7) were detected by quantitative real-time PCR (qRT-PCR) or Western blotting. RNase R and actinomycin D assays were used to assess the stability of hsa_circ_0009035. Cell proliferation, cell cycle progression, apoptosis, migration, and invasion were gauged with Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays. Cell colony formation and survival were determined by the colony formation assay. Targeted correlations among hsa_circ_0009035, miR-889-3p, and HOXB7 were examined by the dual-luciferase reporter, RNA immunoprecipitation (RIP), or RNA pulldown assay. Animal studies were performed to evaluate the impact of hsa_circ_0009035 on tumor growth. We found that hsa_circ_0009035 was highly expressed in CC tissues and cells, and it was associated with the radioresistance of CC patients. Moreover, the silencing of hsa_circ_0009035 inhibited CC cell proliferation, migration, invasion, and it enhanced apoptosis and radiosensitivity in vitro and weakened tumor growth in vivo. Mechanistically, hsa_circ_0009035 directly targeted miR-889-3p by binding to miR-889-3p, and hsa_circ_0009035 modulated HOXB7 expression through miR-889-3p. HOXB7 was a functional target of miR-889-3p in regulating CC progression and radioresistance in vitro, and hsa_circ_0009035 modulated CC progression and radioresistance in vitro by miR-889-3p. Our current study first identified hsa_circ_0009035 as an important regulator of CC progression and radioresistance at least in part through targeting the miR-889-3p/HOXB7 axis, highlighting its significance as a potential therapeutic target for CC treatment.

Factors Affecting the Re-Endothelialization of Endothelial Progenitor Cell.

The vascular endothelium, which plays an essential role in maintaining the normal shape and function of blood vessels, is a natural barrier between the circulating blood and the vascular wall tissue. The endothelial damage can cause vascular lesions, such as atherosclerosis and restenosis. After the vascular intima injury, the body starts the endothelial repair (re-endothelialization) to inhibit the neointimal hyperplasia. Endothelial progenitor cell is the precursor of endothelial cells and plays an important role in the vascular re-endothelialization. However, re-endothelialization is inevitably affected in vivo and in vitro by factors, which can be divided into two types, namely, promotion and inhibition, and act on different links of the vascular re-endothelialization. This article reviews these factors and related mechanisms.

Human p21-activated kinase 5 (PAK5) expression and potential mechanisms in relevant cancers: Basic and clinical perspectives for molecular cancer therapeutics.

An oncogenic role, p21-activated kinase 5 (PAK5), has proven as a significant mediator for many cellular progression, which is expressed highly in human organs such as lung, liver, kidney, blood vessels endothelial cells and inflammatory cells. PAK5 was primitively detected in the cerebrum and accelerated the filopodia formation in neurocytes. It can reverse the effect of Rho and adjust its activity to mediate maintenance and development of nerve axon by binding with Cdc42-GTP. Moreover, PAK5 has been suggested to mediate protean, multitudinous and inscrutable functions in cancer. Currently, many researches indicated that PAK5 was dysregulated in ovarian cancer, cervical cancer, melanoma, osteosarcoma, renal carcinoma, breast cancer, gastric cancer and so on, which was involved in cell proliferation, apoptosis, migration and invasion. This review focuses the latest knowledge on the structure, expression, signalling pathway of PAK5, emphasizing its function in cancer.

Multi-system reproductive metabolic disorder: significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS).

Polycystic ovary syndrome (PCOS), a multisystem disease, is a major reason for female infertility around the world. It is no longer considered simply as a disease of ovary. Now researchers growing awareness of the multisystem features of this disease. PCOS has a higher relationship with metabolic disturbance and hypothalamic-pituitary-ovarian axis (HPOA) function disorders. This syndrome results in hyperandrogenemia (HA), hyperinsulinemia/insulin resistance (IR), increased estrone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) ratio imbalance, infertility, cardiovascular diseases, endometrial dysfunction, obesity, and including a litany of other health issues. Furthermore, PCOS has been garnered in recent times. Interventions like metformin, orlistat, hormonal contraceptives, GLP1 agonists, and VitD have been applied to ameliorate or reverse the pathological characterization of PCOS. Moreover, drug-combined therapy of PCOS is superior to single drug administration. This review will focus on the recent progress in pathogenesis and therapy of PCOS.

Novel Self-assembled Organic Nanoprobe for Molecular Imaging and Treatment of Gram-positive Bacterial Infection.

Background: Increasing bacterial infections as well as a rise in bacterial resistance call for the development of novel and safe antimicrobial agents without inducing bacterial resistance. Nanoparticles (NPs) present some advantages in treating bacterial infections and provide an alternative strategy to discover new antibiotics. Here, we report the development of novel self-assembled fluorescent organic nanoparticles (FONs) with excellent antibacterial efficacy and good biocompatibility. Methods: Self-assembly of 1-(12-(pyridin-1-ium-1-yl)dodecyl)-4-(1,4,5-triphenyl-1H-imidazol-2-yl)pyridin-1-ium (TPIP) in aqueous solution was investigated using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The bacteria were imaged under a laser scanning confocal microscope. We evaluated the antibacterial efficacy of TPIP-FONsin vitro using sugar plate test. The antimicrobial mechanism was explored by SEM. The biocompatibility of the nanoparticles was examined using cytotoxicity test, hemolysis assay, and histological staining. We further tested the antibacterial efficacy of TPIP-FONsin vivo using the S. aureus-infected rats. Results: In aqueous solution, TPIP could self-assemble into nanoparticles (TPIP-FONs) with characteristic aggregation-induced emission (AIE). TPIP-FONs could simultaneously image gram-positive bacteria without the washing process. In vitro antimicrobial activity suggested that TPIP-FONs had excellent antibacterial activity against S. aureus (MIC = 2.0 µg mL-1). Furthermore, TPIP-FONs exhibited intrinsic biocompatibility with mammalian cells, in particular, red blood cells. In vivo studies further demonstrated that TPIP-FONs had excellent antibacterial efficacy and significantly reduced bacterial load in the infectious sites. Conclusion: The integrated design of bacterial imaging and antibacterial functions in the self-assembled small molecules provides a promising strategy for the development of novel antimicrobial nanomaterials.

[Cognitive profile of children with newly onset benign epilepsy with centro-temporal spikes before treatment:a study of computerized cognitive testing in epilepsy].

OBJECTIVE: Benign epilepsy with centro-temporal spikes (BECTs) is a common idiopathic partial epileptic syndrome in childhood, which often affect the pre-school and school-age children and a considerable proportion have comorbidity including lower academic achievement and cognitive impairment. Few studies involved the psychocognitive assessment in such a drug-treatable epileptic syndrome especially in the newly diagnosed and medications-naive group. This study aimed to investigate the cognitive characteristics of children with newly onset BECTs before treatment. METHOD: Forty-one outpatients with newly diagnosed BECTs who visited the Clinic during the periods from October 2012 to May 2014 before the medications against epilepsy and 41 healthy controls recruited from regular school in Beijing during the period from July 2013 to March 2014, who matched in age and gender underwent battery testing by computerized cognitive testing in epilepsy (CCTE). The BECTs group included 41 children, 20 boys and 21 girls, mean age (8.2 ± 1.7) years, the age of onset of epilepsy 4.5-11.5 years (the age of onset <8 years in 25 cases, ≥ 8 years in 16 cases). The cognitive characteristics and associated factors were analyzed. The primary data including correct answer numbers and reaction times were analyzed by independent sample t-test between the two groups of children with BECTs and healthy controls based on SPSS 18.0 statistical software. RESULT: Raw data of 9 tasks' scores collected from BECTs and healthy control children were continuous variables in accordance with normal distribution. BECTs children performed significantly worse than controls in choice reaction time ((618+158) vs. (524+254) ms), three-dimensional mental rotation (11 ± 10 vs. 18 ± 12) and visual tracing (10 ± 6 vs.15 ± 6), t=2.01, 3.03 and 3.47, P<0.05, <0.01 and <0.001, respectively.While other 6 tasks showed no significant difference between the two groups (P>0.05 for all comparisons). BECTs boys performed significantly worse than girls on simple substraction tasks compared with standard nine score ((4.7 ± 1.5) vs. (5.6 ± 1.2), t=-2.24, P<0.05). Other 8 tasks showed no significant difference between boys and girls (P>0.05 for all comparisons). Other 9 tasks showed no significant differences between the two groups of BECTs children whose age of onset was before 8 years and those who started seizure ≥ 8 years (P all >0.05). The standard nine scores of simple substraction from the three BECTs groups of dominance sides of spikes and waves during NREM showed significant difference (P<0.05). BECTs children with bilateral discharges performed significantly worse than the other two groups dominantly right or left discharges (4.7 ± 1.2 vs. 6.0 ± 1.2 vs. 4.9 ± 1.4, P all <0.05). There was no significant difference between the two groups with right and left side dominance discharges (P>0.05). Other 8 tasks showed no significant differences among the three groups (P>0.05 for all comparisons). CONCLUSION: Although EEG discharges index below 50% during NREM period, while newly diagnosed BECTs children before treatment with medications against epilepsy performed poorer on tasks of choice reaction time, three-dimensional mental rotation, and visual tracing. The two factors of male and bilateral discharges during NREM period correlate with dysfunction of simple subtraction, the mechanism needs further study and the cognitive function of epilepsy children should be evaluated and followed up, in order to provide psychologic baseline data for persistent cognitive disturbance.