Comparative transcriptome profiling reveals RNA splicing alterations and biological function in patients exposed to occupational noise.

Genetic factors play an important role in susceptibility to noise-induced hearing loss (NIHL). Alternative splicing (AS) is an essential mechanism affecting gene expression associated with disease pathogenesis at the post-transcriptional level, but has rarely been studied in NIHL. To explore the role of AS in the development of NIHL, we performed a comprehensive analysis of RNA splicing alterations by comparing the RNA-seq data from blood samples from NIHL patients and subjects with normal hearing who were exposed to the same noise environment. A total of 356 differentially expressed genes, including 23 transcription factors, were identified between the two groups. Of particular note was the identification of 56 aberrant alternative splicing events generated by 41 differentially expressed genes between the two groups, with exon skipping events accounting for 54% of all the differentially alternative splicing (DAS) events. The results of functional enrichment analysis showed that these intersecting DAS genes and differentially expressed genes were significantly enriched in autophagy and mitochondria-related pathways. Together, our findings provide insights into the role of AS events in susceptibility and pathogenesis of NIHL.

Mesenchymal Stem Cell Exosomal miR-146a Mediates the Regulation of the TLR4/MyD88/NF-κB Signaling Pathway in Inflammation due to Diabetic Retinopathy.

Diabetic retinopathy (DR) is the main cause of vision loss in diabetic patients, which cannot be completely resolved by typical blood sugar control. Inflammation influences the development of DR, so reducing the inflammatory response in DR patients is crucial to the prevention of DR. Therefore, we explored the regulatory effect of bone marrow mesenchymal stem cell (BMSC) exosomes on inflammation in DR mice. In order to analyze the mechanism of action, we used BMSC exosomal miR-146a to treat microglias in DR mice to observe cellular changes and expression of inflammatory factors. It was found that BMSC exosomal miR-146a reduced the levels of proliferating cell antigen and B-cell lymphoma-2 in microglias of DR mice and increased Bcl-2-related X with cysteine aspartic protease-3. By analyzing the expression of inflammatory factors, we found that BMSC exosomal miR-146a reduced the levels of TNF-α, IL-1ß, and IL-6, which suggested that miR-146a can alleviate inflammation in DR mice. Further exploration found that miR-146a reduced the activity of TLR4 and increased the activity of MyD88 and NF-κB. Furthermore, the overexpression of TLR4 reversed the effects of miR-146a on the proliferation, apoptosis, and inflammation of microglias. Our study demonstrated that BMSC exosomal miR-146a can regulate the inflammatory response of DR by mediating the TLR4/MyD88/NF-κB pathway, providing an experimental basis for the prevention and treatment of DR.

MiR-192 attenuates high glucose-induced pyroptosis in retinal pigment epithelial cells via inflammasome modulation.

Diabetic retinopathy is one of the most characteristic complications of diabetes mellitus, and pyroptosis plays acrucial role in the onset and development of diabetic retinopathy. Although microRNA-192 (miR-192) has been demonstrated to be involved in diabetic retinopathy progression, to the best of our knowledge, its potential and mechanism in cell pyroptosis in diabetic retinopathy have not been studied. The present study demonstrated that high glucose (HG) contributes to the pyroptosis of retinal pigment epithelial (RPE) cells in a dose-dependent manner. The results revealed that miR-192 was weakly expressed in HG-induced RPE cells. Furthermore, overexpression of miR-192 abrogated the role of HG in RPE cell pyroptosis. Based on the bioinformatics analysis, a dual-luciferase reporter assay, and an RNA pull-down assay, FTO α-ketoglutarate-dependent dioxygenase (FTO) was demonstrated to be a direct target of miR-192. Additionally, upregulation of FTO abolished the effects of miR-192 on RPE cells treated with HG. Nucleotide-binding domain leucine-rich repeat family protein 3 (NLRP3) inflammasome activation is vital for cell pyroptosis, and FTO functions as a pivotal modulator in the N6-methyladenosine modifications of various genes. Mechanistically, FTO enhanced NLRP3 expression by facilitating demethylation of NLRP3. In conclusion, the present results demonstrate that miR-192 represses RPE cell pyroptosis triggered by HG via regulation of the FTO/NLRP3 signaling pathway.

Nanofluorescence Probes to Detect miR-192/Integrin Alpha 1 and Their Correlations with Retinoblastoma.

We developed a novel nanostructure DNA probe for the in situ detection of ITGA1 and miR-192 in retinoblastoma (RB) and to study the correlation between ITGA1 and miR-192 expression and RB development. ITGA1 and miR-192 nanostructure DNA probes were carried by silica particles and coated by dioleoyl-trimethy-lammonium-propane, which enhances their organizational compatibility and infiltration capacity. This probe has stable physicochemical properties and high specificity and sensitivity to detect ITGA1 and miR-192 in situ both in RB cell lines and RB tissues. Using ITGA1 and miR-192 nanostructure DNA probes in RB tissue and cell lines, we found that the expression of ITAG1 drastically increased, but to the contrary, miR-192 was not expressed. After transfection, ITGA1 and miR-192 were overexpressed or silenced in RB116 cells, and we found that ITGA1 could effectively increase the activity and invasion of this RB cell line and reduce its apoptosis level, while miR-192 antagonized this tumor-promoting effect. Therefore, miR-192 can be used as an early biomarker of RB, and ITGA1 may be a new prognostic marker and therapeutic target for the treatment of RB.

Statistical Learning Methods Applicable to Genome-Wide Association Studies on Unbalanced Case-Control Disease Data.

Despite the fact that imbalance between case and control groups is prevalent in genome-wide association studies (GWAS), it is often overlooked. This imbalance is getting more significant and urgent as the rapid growth of biobanks and electronic health records have enabled the collection of thousands of phenotypes from large cohorts, in particular for diseases with low prevalence. The unbalanced binary traits pose serious challenges to traditional statistical methods in terms of both genomic selection and disease prediction. For example, the well-established linear mixed models (LMM) yield inflated type I error rates in the presence of unbalanced case-control ratios. In this article, we review multiple statistical approaches that have been developed to overcome the inaccuracy caused by the unbalanced case-control ratio, with the advantages and limitations of each approach commented. In addition, we also explore the potential for applying several powerful and popular state-of-the-art machine-learning approaches, which have not been applied to the GWAS field yet. This review paves the way for better analysis and understanding of the unbalanced case-control disease data in GWAS.

The clinical research into the application of multifunctional airbag abdominal pressure belt in midwifery and in the prevention of postpartum hemorrhage.

OBJECTIVE: Explore the effect of the multifunctional airbag abdominal pressure belt on midwifery and on the prevention of postpartum hemorrhage. METHODS: Select 363 natural delivery cases of hospitalized primiparae and divide them randomly into two groups. In the observation group, 182 primiparae used the multifunctional airbag abdominal pressure belt during the second and third stages of labor, whereas the control group of 181 did not use the belt. Delivery outcomes of the primiparae and their fetus were then observed. RESULTS: The average duration for the second stage of labor, from head emergence to delivery, placenta delivery and postpartum hemorrhage were all shorter in the observation group (p < 0.01). There was no statistical difference in episiotomy rate, maternal signs 2 h postpartum, neonatal Apgar score and neonatal cord blood gas analysis (p > 0.05). No statistical difference was found in primipara signs and no fetal heart rate change of the primiparae under different internal pressures of the belt during the second stage of labor in the observation group (p > 0.05). CONCLUSION: By closely monitoring and appropriately adjusting the internal pressure of the belt, the multifunctional airbag abdominal pressure belt can speed up the second and third stages of labor, prevent postpartum hemorrhage and promote natural delivery.

A facile synthesis of molybdenum carbide nanoparticles-modified carbonized cotton textile as an anode material for high-performance microbial fuel cells.

A novel macroscale porous structure electrode, molybdenum carbide nanoparticles-modified carbonized cotton textile (Mo2C/CCT), was synthesized by a facile two-step method and used as an anode material for high-performance microbial fuel cells (MFCs). The characterization results show that the carbonized cotton textile modified with Mo2C nanoparticles offers a great specific surface area (832.17 m2 g-1) for bacterial adhesion. The MFC using Mo2C/CCT anode delivers the maximum power density of 1.12 W m-2, which is 51% and 116% higher than that of CCT and unmodified carbon felt anodes under the same conditions. The high power density is mainly due to the Mo2C nanoparticles with good biocompatibility and high conductivity and superior electrochemical activity, as well as the macroscale porous structure of carbonized cotton textile, which facilitate the formation of electroactive biofilm and improve the electron transfer. This paper introduces a feasible way to synthesize cost-effective and high-performance anode materials for MFCs.

Effect of Carbon Sources on the Catalytic Performance of Ni/ß-Mo2C.

In this paper, Ni/ß-Mo2C(S) and Ni/ß-Mo2C(G) were prepared from solution-derived precursor with two different carbon sources (starch and glucose) and tested as anodic noble-metal-free catalysts in air-cathode microbial fuel cells (MFCs). The carburized catalyst samples were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET). The activity of the electrocatalyst towards the oxidation of several common microbial fermentation products (formate, lactate, and ethanol) was studied for MFC based on Klebsiella pneumoniae conditions. The composite MFC anodes were fabricated, and their catalytic behavior was investigated. With different carbon sources, the crystalline structure does not change and the crystallinity and surface area increase. The electrocatalytic experiments show that the Ni/ß-Mo2C(G) gives the better bio- and electrocatalytic performance than Ni/ß-Mo2C(S) due to its higher crystallinity and BET surface area.

Ni3Mo3C as anode catalyst for high-performance microbial fuel cells.

Ni3Mo3C was prepared by a modified organic colloid method and explored as anode catalyst for high-performance microbial fuel cell (MFC) based on Klebsiella pneumoniae (K. pneumoniae). The prepared sample was characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET). The activity of the sample as anode catalyst for MFC based on K. pneumoniae was investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and polarization curve measurement. The results show that the adding of nickel in Mo2C increases the BET surface area of Mo2C and improves the electrocatalytic activity of Mo2C towards the oxidation of microbial fermentation products. The power density of MFC with 3 mg cm(-2) Ni3Mo3C anode is far higher than that of the MFC with carbon felt as anode without any catalyst, which is 19 % higher than that of Mo2C anode and produced 62 % as much as that of Pt anode, indicating that Ni3Mo3C is comparative to noble metal platinum as anode electrocatalyst for MFCs by increasing the loading.

Analysis of prognosis-associated factors in fulminant viral hepatitis during pregnancy in China.

OBJECTIVE: To analyze factors contributing to the prognosis of patients with fulminant viral hepatitis in pregnancy (FVHP). METHODS: A retrospective study was conducted among 90 patients with FVHP who were admitted between January 1994 and August 2008 in 9 Chinese hospitals with expertise in the treatment of FVHP. RESULTS: Different clinical types of FVHP presented with different fatality rates; the acute type showed the highest fatality rate and the chronic type showed the lowest fatality rate. Serum albumin (Alb), total cholesterol (Tch), total bilirubin (Tbil), prothrombin activity (PTA), creatinine (Scr), white blood cell count (WBC), the phenomenon of "bilirubin-transaminase separation", and intractable complications correlated with the prognosis of FVHP. The fatality rate increased with decreasing Tch and PTA, increasing WBC, the appearance of "bilirubin-transaminase separation", and complications such as hepatic encephalopathy, hepatorenal syndrome, hemorrhage, and infection. The above indices were all significantly different between survivor and non-survivor groups. CONCLUSION: The clinical type of fulminant hepatitis, Alb, Tch, PTA, TBIL, Scr WBC, phenomenon of "bilirubin-transaminase separation", and intractable complications are important factors associated with prognosis of patients with FVHP. Dynamic monitoring of these indicators and active treatment of complications are key to the improvement of outcomes in patients with FVHP.

Molybdenum carbide as anodic catalyst for microbial fuel cell based on Klebsiella pneumoniae.

A pure beta-molybdenum carbide (M(O2)C) with a Brunauer-Emmett-Teller (BET) special surface area of 77.5 m2/g, prepared by solution derived precursor, was used as anodic catalyst of microbial fuel cell (MFC) based on Klebsiella pneumoniae (K. pneumoniae). The electrochemical activity of the prepared M(O2)C and the performance of the MFC were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and polarization curve measurement. The results show that the prepared M(O2)C has high electrocatalytic activity and is a potential alternative to platinum as the anodic catalyst of MFCs. The maximum power density of single-cube MFC with 6.0 mg/cm2 M(O2)C as anodic catalyst is 2.39 W/m3. This power density is far higher than that of the MFC with carbon felt as anode without any catalyst (0.61 W/m3), and comparable to that of the MFC using 0.5 mg/cm2 Pt as anodic catalyst (3.64 W/m3).

Theoretical insight into oxidative decomposition of propylene carbonate in the lithium ion battery.

The detailed oxidative decomposition mechanism of propylene carbonate (PC) in the lithium ion battery is investigated using density functional theory (DFT) at the level of B3LYP/6-311++G(d), both in the gas phase and in solvent. The calculated results indicate that PC is initially oxidized on the cathode to a radical cation intermediate, PC(*+), and then decomposes through three pathways, generating carbon dioxide CO(2) and radical cations. These radical cations prefer to be reduced on the anode or by gaining one electron from PC, forming propanal, acetone, or relevant radicals. The radicals terminate by forming final products, including trans-2-ethyl-4-methyl-1,3-dioxolane, cis-2-ethyl-4-methyl-1,3-dioxolane, and 2,5-dimethyl-1,4-dioxane. Among all the products, acetone is most easily formed. The calculations in this paper give detailed explanations of the experimental findings that have been reported in the literature and clarify the role of intermediate propylene oxide in PC decomposition. Propylene oxide is one of the important intermediates. As propylene oxide is formed, it isomerizes forming a more stabile product, acetone.