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The long non-coding RNA, Negative Regulator of Antiviral Response (NRAV) has been identified as a participant in both respiratory virus replication and immune checkpoints, however, its involvement in pan-cancer immune regulation and prognosis, particularly those of hepatocellular carcinoma (HCC), remains unclear. To address this knowledge gap, we analyzed expression profiles obtained from The Cancer Genome Atlas (TCGA) database, comparing normal and malignant tumor tissues. We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues. Kaplan-Meier (K-M) analysis revealed the prognostic power of NRAV, wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients. Furthermore, noteworthy associations were observed between NRAV, immune checkpoints, immune cell infiltration, genes related to autophagy, epithelial-mesenchymal transition (EMT), pyroptosis, tumor mutational burden (TMB), and microsatellite instability (MSI) across different cancer types, including HCC. Moreover, NRAV upregulation expression was associated with multiple pathological stages by clinical observations. Furthermore, our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells. The inhibition of NRAV resulted in the inhibition of cell proliferation, migration, and invasion in HCC cells, while also influencing the expression of CD274 (PD-L1) and CD44, along with various biomarkers associated with EMT, autophagy, and pyroptosis. The aforementioned results propose NRAV as a promising prognostic biomarker for HCC. [ABSTRACT FROM AUTHOR]

Novel the bilayered electrospun biosheet with rapid cell mimiciking and proliferative efficacy will be suitable for wound healing application. The optimized concentration of gelatin (G) and sodium alginate (A) biosheet with nanofibrous Poly (3-hydroxybutyric acid) (P) as a bilayered elctrospun matrix through electrospinning. The engineered GAP bilayered biosheet involves tissue formation at extra cellular matrix (ECM) which further characterized its function in vitro and invivo. Here we fabricated GAP which exhibit better physiochemical properties, biological and mechanical properties with superior prosomes it enhance air passable at skin wounds. The Bilayered biosheet matrix possess better biocompatibility, cell adherence, fructuous and cell to cell interactions evaluated using cell lines. Furthermore, GAP bilayered matrix regulates growth factors to attain maximum wound closure efficiency during invivo. Thus, the fabricated GAP electrospun biosheet would be a possible wound dressing for skin wound applications. [ABSTRACT FROM AUTHOR]

The olfactory system receives extensive serotonergic inputs from the dorsal raphe, a nucleus involved in control of behavior, regulation of mood, and modulation of sensory processing. Although many studies have investigated how serotonin modulates the olfactory bulb, few have focused on the anterior piriform cortex (aPC), a region important for olfactory learning and encoding of odor identity and intensity. Specifically, the mechanism and functional significance of serotonergic modulation of the aPC remain largely unknown. Here we used pharmacologic, optogenetic, and fiber photometry techniques to examine the serotonergic modulation of neural activity in the aPC in vitro and in vivo. We found that serotonin (5-HT) reduces the excitability of pyramidal neurons directly via 5-HT2C receptors, phospholipase C, and calcium-activated potassium (BK) channels. Furthermore, endogenous serotonin attenuates odor-evoked calcium responses in aPC pyramidal neurons. These findings identify the mechanism underlying serotonergic modulation of the aPC and shed light on its potential role. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs), the largest family of targets for approved drugs, are rarely targeted for cancer treatment, except for certain endocrine and hormoneresponsive tumors. Limited knowledge regarding GPCR expression in cancer cells likely has contributed to this lack of use of GPCR-targeted drugs as cancer therapeutics. We thus undertook GPCRomic studies to define the expression of endoGPCRs (which respond to endogenous molecules such as hormones, neurotransmitters and metabolites) in multiple types of cancer cells. Using TaqMan qPCR arrays to quantify the mRNA expression of ~340 such GPCRs, we found that human chronic lymphocytic leukemia (CLL) cells/stromal cells associated with CLL, breast cancer cell lines, colon cancer cell lines, pancreatic ductal adenocarcinoma (PDAC) cells, cancer associated fibroblasts (CAFs), and PDAC tumors express 50 to >100 GPCRs, including many orphan GPCRs (which lack known physiologic agonists). Limited prior data exist regarding the expression or function of most of the highly expressed GPCRs in these cancer cells and tumors. Independent results from public cancer gene expression databases confirm the expression of such GPCRs. We propose that highly expressed GPCRs in cancer cells (for example, GPRC5A in PDAC and colon cancer cells and GPR68 in PDAC CAFs) may contribute to the malignant phenotype, serve as biomarkers and/or may be novel therapeutic targets for the treatment of cancer. [ABSTRACT FROM AUTHOR]

To evaluate the environmental effectiveness of the control measures for atmospheric pollution in Shijiazhuang of China, a large-scale controlling experiment for emission sources of atmospheric pollutants (i.e., a temporary emission control action, TECA) was designed and implemented during November 1, 2016 to January 9, 2017. Under the unfavorably meteorological conditions, the mean concentrations of PM2.5, PM10, SO2, NO2, and chemical species (Si, Al, Ca2+, Mg2+) in PM2.5 during the control action and heating period (CAHP) still decreased by 15%, 26%, 5%, 19%, 30.3%, 4.5%, 47.0% and 45.2%, respectively, compared to the no control action and heating period (NCAHP); indicating that the control measures of atmospheric pollution in Shijiazhuang were effective and was in a right direction. Overall, the effects of control measures in suburbs were better than those in urban area, especially for the control effects of particulate matters sources. The control effects for emission sources of carbon monoxide (CO) were not apparent during the TECA period, especially in suburbs, which is likely due to the increasing usage of domestic coal in suburbs along with the temperature decreasing. The results of PMF analysis showed that crustal dust, secondary sources, vehicle emissions, coal combustion and industrial emissions were major PM2.5 sources. Compared to the whole year, the contributions of coal combustion to PM2.5 increased significantly during the CAHP and after control action (ACA); while the contribution proportions of crustal dust and vehicle emissions to PM2.5 decreased apparently during the CAHP. The contribution concentrations and proportions of crustal dust and vehicle emissions to PM2.5 during the CAHP also decreased significantly compared to ACA. The pollutant's emission sources during the CAHP were in effective control, especially for crustal dust and vehicles. While the necessary coal heating for cold winter and the unfavorably meteorological conditions had an offset effect on the control measures for emission sources to some extent. Meanwhile, our results also illustrated that the discharge of pollutants was still enormous even under such strict control measures. The backward trajectory and potential source contribution function (PSCF) analysis in the light of atmospheric pollutants suggested that the potential sources-areas mainly concentrated in surrounding regions of Shijiazhuang, i.e., south of Hebei, north of Henan and Shanxi. The regional nature of the atmospheric pollution in Northern China Plain revealed that there is an urgent need for making cross-boundary control policy except for local control-measures given the high background level of pollutants. The TECA is an important practical exercise but it can't be advocated as the normalized control measures for atmospheric pollution in China. The direct cause of atmospheric pollution in China is the emission of pollutants exceeds the air environment's self-purification capacity, and the essential reason is unreasonable and unhealthy pattern for economic development of China. [ABSTRACT FROM AUTHOR]

Mitochondrial morphology is regulated by fusion and fission machinery. Impaired mitochondria dynamics cause various diseases, including Alzheimer's disease. Appoptosin (encoded by SLC25A38) is a mitochondrial carrier protein that is located in the mitochondrial inner membrane. Appoptosin overexpression causes overproduction of reactive oxygen species (ROS) and caspase-dependent apoptosis, whereas appoptosin downregulation abolishes β-amyloid-induced mitochondrial fragmentation and neuronal death during Alzheimer's disease. Herein, we found that overexpression of appoptosin resulted in mitochondrial fragmentation in a manner independent of its carrier function, ROS production or caspase activation. Although appoptosin did not affect levels of mitochondrial outer-membrane fusion (MFN1 and MFN2), inner-membrane fusion (OPA1) and fission [DRP1 (also known as DNM1L) and FIS1] proteins, appoptosin interacted with MFN1 and MFN2, as well as with the mitochondrial ubiquitin ligase MITOL (also known as MARCH5) but not OPA1, FIS1 or DRP1. Appoptosin overexpression impaired the interaction between MFN1 and MFN2, and mitochondrial fusion. By contrast, co-expression ofMFN1,MITOL and a dominant-negative form of DRP1, DRP1K38A, partially rescued appoptosin-induced mitochondrial fragmentation and apoptosis, whereas co-expression of FIS1 aggravated appoptosin-induced apoptosis. Together, our results demonstrate that appoptosin can interact with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology. [ABSTRACT FROM AUTHOR]

Background: Delivery of antigens by live bacterial carriers can elicit effective humoral and cellular responses and may be an attractive strategy for live bacterial vaccine production through introduction of a vector that expresses an exogenous protective antigen. To overcome the instability and metabolic burden associated with plasmid introduction, alternative strategies, such as the use of in vivo-inducible promoters, have been proposed. However, screening an ideal in vivo-activated promoter with high efficiency and low leak expression in a particular strain poses great challenges to many researchers. Results: In this work, we constructed an in vivo antigen-expressing vector suitable for Edwardsiella tarda, an enteric Gram-negative invasive intracellular pathogen of both animals and humans. By combining quorum sensing genes from Vibrio fischeri with iron uptake regulons, a synthetic binary regulation system (ironQS) for E. tarda was designed. In vitro expression assay demonstrated that the ironQS system is only initiated in the absence of Fe2+ in the medium when the cell density reaches its threshold. The ironQS system was further confirmed in vivo to present an in vivo-triggered and cell density-dependent expression pattern in larvae and adult zebrafish. A recombinant E. tarda vector vaccine candidate WED(ironQS-G) was established by introducing gapA34, which encodes the protective antigen glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the fish pathogen Aeromonas hydrophila LSA34 into ironQS system, and the immune protection afforded by this vaccine was assessed in turbot (Scophtalmus maximus). Most of the vaccinated fish survived under the challenge with A. hydrophila LSA34 (RPS = 67.0%) or E. tarda EIB202 (RPS = 72.3%). Conclusions: Quorum sensing system has been extensively used in various gene structures in synthetic biology as a well-functioning and population-dependent gene circuit. In this work, the in vivo expression system, ironQS, maintained the high expression efficiency of the quorum sensing circuit and achieved excellent expression regulation of the Fur box. The ironQS system has great potential in applications requiring in vivo protein expression, such as vector vaccines. Considering its high compatibility, ironQS system could function as a universal expression platform for a variety of bacterial hosts. [ABSTRACT FROM AUTHOR]

Cyclic nucleotide phosphodiesterase (POE) isoforms can influence disease pathogenesis and be novel therapeutic targets. Because lower cAMP levels may contribute to the decreased apoptosis that occurs in chronic lymphocytic leukemia (CLL), we assessed the expression levels of POE isoforms in peripheral blood mononuclear cells (PBMC) of healthy adults and patients with CLL. We found a unique POE mRNA signature in CLI: higher levels than in normal PBMC of PDE7B (increased ≈23-fold) and lower levels of PDE3B, 4D, 5A, and 9A mRNA (each decreased ≈30-fold). Increased POE7B mRNA in CLL correlates with a 10-fold-higher expression of PDE7B protein and results in an increased contribution of PDE7 to total PDE activity. Consistent with the higherlevel of PDE7B expression, inhibitors of PDE7 (BRL-50481, IR-202) and a dual PDE4/PDE7 inhibitor (IR-284) selectively increase apoptosis in CLI cells compared with normal PBMC or B cells. Apoptosis of CLI cells promoted by inhibitors of PDE7 and PDE4I7 is attenuated by PKA inhibition, occurs via a mitochondrial-dependent process, and is associated with increased cAMP accumulation and down-regulation of the antiapoptotic protein survivin and of PDE7B. The increase in PDE7B expression and PDE7 inhibitor-promoted apoptosis implicates PDE7B as a drug target in CLI. Our findings identify a unique PDE signature in CLL and illustrate the utility of broad analyses of POE isoform expression in human disease. [ABSTRACT FROM AUTHOR]

Monomethyl ethers of oligoethylene glycols with different chain lengths were converted to trimethylsilyl derivatives by reacting with trimethylchlorosilane in the presence of triethylamine, or by directly refluxing with excess trimethylchlorosilane or hexamethyldisilazane. Similarly, two oligoethylene glycols were converted to bis(trimethylsilyl) derivatives. When doped with lithium bis(trifluoromethanesulfonyl)imide, these electrolytes have very high conductivity, generally >10−3 S cm−1. A full cell performance test using one of these new electrolytes (1NM3) showed excellent cyclability at room temperature. Introducing a second trimethylsilyl group decreases the conductivity of trimethylsilylated compounds. The thermal properties, viscosities and dielectric constants of the compounds were measured, and the effect of those on the conductivity is reported. Cyclic voltammetry experiments show that the trimethylsilylated compound (1NM2) of diethylene glycol monomethyl ether has greater electrochemical stability than its germanium and carbon analogues. [ABSTRACT FROM AUTHOR]

The effects of synthesis parameters on the activity of Co–ZrO2 catalysts in bio-ethanol steam reforming (BESR) were investigated. The supported catalysts were prepared by incipient wetness impregnation (IWI) and characterized through N2 physisorption, H2 chemisorption, X-ray diffraction, X-ray photoelectron spectroscopy, temperature programmed calcination, temperature programmed reduction, temperature programmed oxidation, thermogravimetric analysis, ethanol pulse chemisorption, and temperature programmed reaction techniques. The synthesis parameters examined include calcination temperature, reduction temperature, and reduction time. The catalyst evolution at different stages of the synthesis process was investigated. The ethanol adsorption and temperature programmed reaction experiments indicated a strong correlation between the catalytic activity and metallic cobalt surface area for the 10 wt% Co–ZrO2 catalyst. [ABSTRACT FROM AUTHOR]

Although a substantial number of hormones and drugs increase cellular CAMP levels, the global impact of CAMP and its major effector mechanism, protein kinase A (PKA). on gene expression is not known. Here we show that treatment of murine wild-type 549 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (8-CPT- CAMP), a PKA-selective cAMP analog, alters the expression of ≈4,500 of ≈ 13,600 unique genes. By contrast, gene expression was unaltered in Kin- 549 cells (that lack PKA) incubated with 8-CPT- CAMP. Changes in mRNA and protein expression of several cell- cycle regulators accompanied cAMP-induced G1-phase cell-cycle arrest of wild-type S49 cells. Within 2 h, 8-CPT-cAMP altered expression of 152 genes that contain evolutionarily conserved cAMP-response elements within 5 kb of transcriptional start sites, including the circadian clock gene Pen. Thus, CAMP through its activation of PKA produces extensive transcriptional regulation in eukaryotic cells. These transcriptional networks include a primary group of cAMP-response element-containing genes and secondary networks that include the circadian clock. [ABSTRACT FROM AUTHOR]

Examines the role of Bcl-2 in protecting lymphoma cells from apoptosis. Insignificance of Bcl-2 in protecting growth arrest by cAMP and dexamethasone; Decrease in cell number without affecting viability; Manifestation of cell growth pattern different from wild-type S49 cells.