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Ubiquitinlation of proteins is prevalent and important in both normal and pathological cellular processes. Deubiquitinating enzymes (DUBs) can remove the ubiquitin tags on substrate proteins and dynamically regulate the ubiquitination process. The PPPDE family proteins were predicted to be a novel class of deubiquitinating peptidase, but this has not yet been experimentally proved. Here we validated the deubiquitinating activity of PPPDE1 and revealed its isopeptidase activity against ubiquitin conjugated through Lys 48 and Lys 63. We also identified ribosomal protein S7, RPS7, as a substrate protein of PPPDE1. Moreover, PPPDE1 could mediate the ubiquitin chain editing of RPS7, deubiquitinating Lys 48-linked ubiquitination, and finally stabilize RPS7 proteins. Taken together, we report that PPPDE1 is a novel deubiquitinase that belongs to a cysteine isopeptidase family. [ABSTRACT FROM AUTHOR]

Tris (2-butoxyethyl) phosphate (TBOEP) is widely used as a substitute of polybrominated diphenyl ethers (PBDEs). It has been frequently measured at concentrations of micrograms per liter (μg/L) in surface waters and waste water. However, limited information is available about the reproduction toxicology of TBOEP. In this study, adult zebrafish pairs were exposed to TBOEP at concentrations of 0, 5, 50, and 500 μg/L for 21 days. The effects on reproduction, hormone concentration, transcription of genes along the hypothalamic-pituitary-gonadal (HPG) axis, and gonadal development were investigated. After exposure to TBOEP, plasma concentrations of 17β-estradiol were significantly increased in both sexes of fish, while increase of testosterone was observed only in male fish. Transcription of genes along the HPG axis was significantly influenced by exposure to TBOEP in both male and female fish. Moreover, TBOEP decreases the average number of eggs production, as well as hatching success and survival rates in offspring. Histological examination shows inhibition of oocyte maturation in females and retardation spermiation in males, respectively. The results demonstrate that TBOEP could disturb the sex hormone balance by altering regulatory circuits of the HPG axis, affect gonadal development, eventually leading to disruption of reproductive performance and the development of progeny. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that cyanobacteria-derived Microcystin-LR (MC-LR) can cause developmental toxicity and trigger apoptosis in zebrafish ( Danio rerio ) larvae, but the underlying mechanisms remain largely unknown. In this study, we tested the hypothesis that the mechanism by which MC-LR induces developmental toxicity is through activation of endoplasmic reticulum (ER) stress. MC-LR (4.0 μM) exposure through submersion caused serious developmental toxicity, such as malformation, growth delay and decreased heart rates in zebrafish larvae, which could be inhibited by ER stress blocker, tauroursodeoxycholic acid (TUDCA, 20 μM). Meanwhile, acridine orange (AO) staining showed TUDCA could rescue cell apoptosis in heart area in zebrafish larvae resulted by MC-LR exposure. Real-time polymerase chain reaction (real-time PCR) analysis demonstrated that MC-LR induced activation of ER stress which consequently triggered apoptosis in zebrafish larvae. Protein expression examined by western blot indicated that MC-LR could activate MAPK8/Bcl-2/Bax pathway and caspase-dependent apoptotic pathway in zebrafish larva and the effects were mitigated by inhibition of ER stress. Taken together, the results observed in this study suggested that ER stress plays a critical role in developmental toxicity and apoptosis in zebrafish embryos exposed to MC-LR. [ABSTRACT FROM AUTHOR]

Bacillus subtilis is frequently used commercially in rice-crayfish coculture system (RCCS) to modify the physicochemical characteristics of soil and water. However, given the intensification of cadmium (Cd) contamination in RCCS and potential implications for food safety, the impacts of this modulation on the Cd bioavailability and accumulation need to be more thoroughly assessed. Here, B. subtilis was inoculated into RCCS containing different levels of soil Cd through an outdoor mesocosm experiment. Results showed that the abundance of B. subtilis in the soil was highest on the 1st day after inoculation and appeared the second peak on the 2nd week. 40–128-fold increase in B. subtilis abundance in crayfish intestines was found in the B. subtilis added groups compared to the non- B. subtilis added groups. Additionally, the Cd accumulation in crayfish and rice tissues rose significantly when the soil Cd content raised. However, with the improvement of soil pH, oxidation-reduction potential (ORP), nitrification potential (NP), acid volatile sulfide (AVS) and sulfur reducing bacteria abundance, and the decrease of organic matter (OM) at 2 W and 8 W, the addition of B. subtilis into RCCS with various Cd contents significantly reduced the Cd accumulation and the soil Cd bioavailability. The low bioavailability of Cd was characterized by the reduction of exchangeable Cd (EXC-Cd) and the grows of Fe–Mn oxides bound Cd (FeMnOx-Cd) and residual Cd (RES-Cd). Specifically, the soil EXC-Cd was negatively correlated with soil pH (−0.647), OPR (−0.663) and NP (−0.811). In short, the obtained results demonstrated that B. subtilis was able to stabilize the physicochemical properties of soil and water in RCCS, while mineralizing Cd and attenuating Cd accumulation in the crayfish and rice, suggesting that B. subtilis can be used as a cleaning probiotic applied in rice and aquatic animals coculture system. [Display omitted] • Application of B. subtilis mitigated RCCS Cd accumulation in Cd-polluted soil. • The stable colonization of B. subtilis in crayfish gut might limit Cd absorption. • B. subtilis inhibited soil Cd bioactivity by improving physicochemical properties. • The supply of B. subtilis also played a vital part in Cd mineralization. [ABSTRACT FROM AUTHOR]

• KrasV12 transgenic zebrafish was used to study the promoting effect of liver tumor. • MC-LR aggravates the progression of HCC at an environmentally relevant level. • Exposure to MC-LR decreased activity of protein phosphatase 2A. • Activation of Wnt signaling by MC-LR might be responsible for HCC promotion. Microcystin-LR (MC-LR) is a kind of natural toxin which exists widely in aquatic environments and has been reported to be hepatotoxic and carcinogenic. At present, the promoting mechanism of MC-LR on hepatocellular carcinoma (HCC) remains largely unexplored. In this study, the hepatocellular promoting effect of MC-LR was described in KrasV12 transgenic zebrafish, a doxycycline (DOX) inducible HCC model. Our results showed that MC-LR could aggravate the progression of HCC at an environmentally relevant concentration (3 μg/L), which was accompanied by the decreased activity and down-regulated transcription level of serine/threonine phosphatase 2A (PP2A). Using TMT labeling quantitative phosphoproteomics, we found that the 1049 phosphopeptides were significantly changed (508 up-regulated and 541 down-regulated) in liver from combined exposure to DOX and 3 μg/L MC-LR group compared to the DOX group. Enriched pathways by KEGG analysis suggested that differentially phosphorylated proteins were mainly related to Wnt signaling pathway. Furthermore, the mRNA expression and protein abundance of β-Catenin in Wnt signaling pathway were significantly up-regulated following exposure to MC-LR. In short, our results suggested that MC-LR significantly inhibited the activity of PP2A, which in turn activated Wnt signaling, eventually resulting in progression of liver tumor in transgenic zebrafish. [ABSTRACT FROM AUTHOR]

An abstract of the article "Transgenic Vasoactive Intestinal Peptide Shows Local Disease Modifying Effects in a Murine Model of Sjögren's Syndrome," by Beatrijs M. Lodde and colleagues is presented.

An abstract of the article "The Effect of Serine Protease Inhibitor 6 (SPI-6) Gene Transfer on a Mouse Model of Sjögren's Syndrome," by Fumi Mineshiba, Beatrijs M. Lodde, Jianghua Wang, Livia A. Casciola-Rosen, Antony Rosen, and Bruce J. Baum is presented.

Although Notch signaling is deregulated in prostate cancer, the role of this pathway in disease development and progression is not fully understood. Here, we analyzed 2 human prostate cancer data sets and found that higher Notch signaling correlates with increased metastatic potential and worse disease survival rates. We used the Pten-null mouse prostate cancer model to investigate the function of Notch signaling in the initiation and progression of prostate cancer. Disruption of the transcription factor RBPJ in Pten-null mice revealed that endogenous canonical Notch signaling is not required for disease initiation and progression. However, augmentation of Notch activity in this model promoted both proliferation and apoptosis of prostate epithelial cells, which collectively reduced the primary tumor burden. The increase in cellular apoptosis was linked to DNA damage-induced p53 activation. Despite a reduced primary tumor burden, Notch activation in Pten-null mice promoted epithelial-mesenchymal transition and FOXC2-dependent tumor metastases but did not confer resistance to androgen deprivation. Notch activation also resulted in transformation of seminal vesicle epithelial cells in Pten-null mice. Our study highlights a multifaceted role for Notch signaling in distinct aspects of prostate cancer biology and supports Notch as a potential therapeutic target for metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Background/Aims: Elucidation of the molecular mechanisms governing osteoblast differentiation and angiogenesis are of great importance for improving the treatment of bone-related diseases. In this study, we examined the role of microRNA (miR)-10a in the differentiation of MC3T3-E1 cells and pro angiogenic activity of mouse umbilical vein endothelial cells (MUVECs). Methods: The murine pre-osteoblast cell line MC3T3-E1 and MUVECs were used in the experiment. After transfected with miR-10a mimics or inhibitors, with or without LiCl pretreatment, the miR-10a, ALP, Runx2, Osx, OC and Dlx5 expression were assessed by RT-PCR. MC3T3-E1 cells were cultured with BMP2 to differentiate into bone cells, osteogenic differentiation of MC3T3-E1 cells were detected by ALP and ARS staining. Cell viability were analyzed by MTT and the protein expression of β-catenin, LEF1, cyclinDl, MMP2, and VEGF were detected by Western blotting; VEGF and VE-cadherin release were assessed by ELISA, and the migration of MUVECs, as well as tube formation were also detected. Results: MiR-10a expression was obviously down-regulated during osteogenic differentiation. Overexpression of miR-10a inhibited osteogenic differentiation of MC3T3-E1 cells, effectively decreasing MUVECs proliferation, migration, VEGF expression, VE-cadherin concentrations, and tube formation in vitro, whereas miR-10a silence enhanced those processes. Further mechanism assays demonstrated that overexpression of miR-10a reduced the β-catenin at both protein and transcription level, while pretreatment with Wnt signaling activator Licl partially attenuated the suppression effects of miR-10a overexpression on osteoblast differentiation and angiogenesis. Conclusion: Our findings imply that miR-10a plays a suppressive role in osteoblast differentiation of MC3T3-E1 cells and pro angiogenic activity of MUVECs by regulating the β-catenin expression, representing a novel and potential therapeutic target for the treatment of bone regeneration-related diseases. [ABSTRACT FROM AUTHOR]

Neurotoxicity of microcystin-leucine-arginine (MCLR) has been widely reported. However, the mechanism is not fully understood. Using primary hippocampal neurons, we tested the hypothesis that MCLR-triggered activation in intracellular free calcium concentration ([Ca2+]i) induces the death of neurons. Microcystin-leucine-arginine inhibited cell viability at a range of 0.1 to 30 μmol/L and caused a dose-dependent increase in [Ca2+]i. This increase in [Ca2+]i was observed in Ca2+-free media and blocked by an endoplasmic reticulum Ca2+ pump inhibitor, suggesting intracellular Ca2+ release. Moreover, pretreatment of hippocampal neurons with intracellular Ca2+ chelator (O,O′-bis (2-aminophenyl) ethyleneglycol-N,N,N′,N′-tetraacetic acid, tetraacetoxy-methyl ester) and inositol 1,4,5-trisphosphate receptor antagonist (2-aminoethoxydiphenyl borate) could block both the Ca2+ mobilization and the neuronal death following MCLR exposure. In contrast, the ryanodine receptor inhibitor (dantrolene) did not ameliorate the effect of MCLR. In conclusion, MCLR disrupts [Ca2+]i homeostasis in neurons by releasing Ca2+ from intracellular stores, and this increase in [Ca2+]i may be a key determinant in the mechanism underlying MCLR-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Currently, there is no effective vaccine to prevent hepatitis C virus (HCV) infection, partly due to our insufficient understanding of the virus glycoprotein immunology. Most neutralizing antibodies (nAbs) were identified using glycoprotein immunogens, such as recombinant E1E2, HCV pseudoparticles or cell culture derived HCV. However, the fact that in the HCV acute infection phase, only a small proportion of patients are self-resolved accompanied with the emergence of nAbs, indicates the limited immunogenicity of glycoprotein itself to induce effective antibodies against a highly evolved virus. Secondly, in previous reports, the immunogen sequence was mostly the genotype of the 1a H77 strain. Rarely, other genotypes/subtypes have been studied, although theoretically one genotype/subtype immunogen is able to induce cross-genotype neutralizing antibodies. To overcome these drawbacks and find potential novel neutralizing epitopes, 57 overlapping peptides encompassing the full-length glycoprotein E1E2 of subtype 1b were synthesized to immunize BALB/c mice, and the neutralizing reactive of the induced antisera against HCVpp genotypes 1–6 was determined. We defined a domain comprising amino acids (aa) 192–221, 232–251, 262–281 and 292–331 of E1, and 421–543, 564–583, 594–618 and 634–673 of E2, as the neutralizing regions of HCV glycoprotein. Peptides PUHI26 (aa 444–463) and PUHI45 (aa 604–618)-induced antisera displayed the most potent broad neutralizing reactive. Two monoclonal antibodies recognizing the PUHI26 and PUHI45 epitopes efficiently precluded genotype 2 viral (HCVcc JFH and J6 strains) infection, but they did not neutralize other genotypes. Our study mapped a neutralizing epitope region of HCV glycoprotein using a novel immunization strategy, and identified two monoclonal antibodies effective in preventing genotype 2 virus infection. [ABSTRACT FROM AUTHOR]

Recent studies have shown that cyanobacteria-derived microcystins (MCs) have the potential to disrupt endocrine systems. However, the effects of microcystin-RR (MC-RR) and their underlying mechanisms are poorly resolved in fish. In this study, MC-RR exposure through submersion caused serious developmental toxicity, such as growth delay and depressed heart rates in zebrafish larvae. We also detected decreased levels of thyroid hormones (THs), suggesting that MC-RR-triggered thyroid endocrine disruption might contribute to the growth impairment observed in developing zebrafish. To further our understanding of mechanisms of MC-RR-induced endocrine toxicity, quantitative real-time PCR (QPCR) analysis was performed on hypothalamic–pituitary–thyroid (HPT) axis related genes, i.e., corticotropin-releasing factor (CRF), thyroid-stimulating hormone (TSH), sodium/iodide symporter (NIS), thyroglobulin (TG), thyroid receptors (TRα and TRβ) and iodothyronine deiodinases (Dio1 and Dio2), of developing zebrafish embryos exposed to 0, 0.3, 1.0 or 3.0 mg L −1 MC-RR until 96 h post-fertilization. Our results showed that transcription pattern of HPT axis related genes were greatly changed by MC-RR exposure, except TG gene. Furthermore, western blot was used to validate the results of gene expression. The results showed protein synthesis of TG was not affected, while that of NIS was significantly up-regulated, which are in accordance with gene expression. The overall results indicated that exposure to MC-RR can induce developmental toxicity, which might be associated with thyroid endocrine disruption in developing zebrafish larvae. [ABSTRACT FROM AUTHOR]

Objective To examine associations between metabolic syndrome (MetS) and its individual components with risk of mild cognitive impairment ( MCI) among community elderly and explore the age difference. Design Cross-sectional study. Subjects About 2 102 aged 60 and older community residents in Beijing metropolitan area, China. Measurements Cognitive function was assessed by Mini-Mental State Examination ( MMSE). MetS was defined by the 2009 harmonizing definition. Overnight-fasting blood samples were obtained to measure biochemistry indicators. Results The prevalence of MetS and MCI was 59·1% and 15·9%, respectively. After adjusting age, gender, other demographic factors, lifestyle variables and medication use, participants with MetS or its individual components are at significantly elevated risk for MCI. In terms of MMSE score, as the continuous dependent variable, the β (95% CI) of MetS was −0·68(−0·99, −0·37). For prevalence of MCI, as the dichotomy dependent variable, the odds ratio ( OR) of Mets is 1·52 compared to control group (or baseline) with 95% confidence interval ( CI) of 1·16 to 1·95. The multivariate association only showed significant results among participants aged less than 80 years old. Conclusions MetS is associated with worse cognitive function among younger elderly. Managing MetS, as well as its components, may contribute to control cognitive decline and reduce related disease and social burden. [ABSTRACT FROM AUTHOR]

This study is designed to follow-up our previous work, in which we demonstrated synergistic and in-situ desulfurization effects during co-disposing shell wastes and an aqueous condensate (AQ) derived from biomass carbonization in combination with coal combustion. The potential use of Ca-enriched coal ash as a coagulant for removing humic acid (HA) from aqueous solution is explored in this study. The HA removal performance of raw and shell-added Datong (DT) coal ashes from aqueous solution is examined and compared with that of commercial aluminum sulfate (alum) and powdered activated carbons (PACs). It is found that shell-added DT ash (DT s ) is markedly superior to both PACs and raw DT ash (DT r ) and is even comparable to alum in terms of HA removal. The excellent HA removal performance of DT s was mainly attributable to the formation of anhydrite and lime during coal combustion. The removal efficiency of HA strongly depends on temperature, initial pH, and DT s dosage. From the results obtained in this study, it is revealed that the calcium-enriched coal ash can be used as an efficient and cost-effective coagulant to treat surface and/or waste waters that are polluted with humic substances. [ABSTRACT FROM AUTHOR]

Context: Celastrol, a natural compound derived from the herb Tripterygium wilfordii, is known to have anticancer activity, but is not soluble in water. Objective: Formation of celastrol liposomes, to avoid the use of toxic solubilising agents. Materials and methods: Two different formulations of PEGylated celastrol liposomes were fabricated. Liposomal characteristics and serum stability were determined using dynamic light scattering. Drug entrapment efficacy and drug release were measured spectrophotometrically. Cellular internalisation and anticancer activity was measured in prostate cancer cells. Results: Liposomal celastrol displayed efficient serum stability, cellular internalisation and anticancer activity, comparable to that of the free drug reconstituted in dimethyl sulfoxide. Discussion and conclusion: Liposomal celastrol can decrease the viability of prostate cancer cells, while eliminating the need for toxic solubilising agents. [ABSTRACT FROM AUTHOR]

Highlights: [•] MCLR-induced apoptosis in the heart of developing embryos leads to the growth delay in zebrafish. [•] MCLR-triggered apoptosis might be induced by ROS. [•] P53–Bax–Bcl-2 and caspase-dependent apoptotic pathway contribute greatly to MCLR-induced apoptosis. [ABSTRACT FROM AUTHOR]

We have investigated the size-dependent high pressure behavior of nanocrystalline TiN using an angle-dispersive X-ray diffraction technique in a diamond-anvil cell at room temperature. No phase transition was observed during compression for each sample. A fit of the pressure versus volume data to a second Birch–Murnaghan equation yielded the following parameters for 16nm, 34nm and 80nm, zero-pressure volume, V 0=75.77Å3, 75.98Å3 and 76.06Å3, bulk modulus, B 0=320(7)GPa, 338(6)GPa and 287(3)GPa, respectively. This result along with a reanalysis of previous studies on TiN indicates that the bulk modulus first increases and then decreases with decreasing grain size. The compressibility of TiN has a minimum at ~34nm. [ABSTRACT FROM AUTHOR]

The TMPRSS2/ERG (T/E) fusion gene is present in the majority of all prostate cancers (PCa). We have shown previously that NF-kB signaling is highly activated in these T/E fusion expressing cells via phosphorylation of NF-kB p65 Ser536 (p536). We therefore hypothesize that targeting NF-kB signaling may be an efficacious approach for the subgroup of PCas that carry T/E fusions. Celastrol is a well known NF-kB inhibitor, and thus may inhibit T/E fusion expressing PCa cell growth. We therefore evaluated Celastrol’s effects in vitro and in vivo in VCaP cells, which express the T/E fusion gene. VCaP cells were treated with different concentrations of Celastrol and growth inhibition and target expression were evaluated. To test its ability to inhibit growth in vivo, 0.5 mg/kg Celastrol was used to treat mice bearing subcutaneous VCaP xenograft tumors. Our results show Celastrol can significantly inhibit the growth of T/E fusion expressing PCa cells both in vitro and in vivo through targeting three critical signaling pathways: AR, ERG and NF-kB in these cells. When mice received 0.5 mg/kg Celastrol for 4 times/week, significant growth inhibition was seen with no obvious toxicity or significant weight loss. Therefore, Celastrol is a promising candidate drug for T/E fusion expressing PCa. Our findings provide a novel strategy for the targeted therapy which may benefit the more than half of PCa patients who have T/E fusion expressing PCas. [ABSTRACT FROM AUTHOR]

Abstract: This study was conducted to evaluate possible bystander effects induced by the model chemical 6-propyl-2-thiouracil (PTU) on melanin synthesis. Zebrafish (Danio rerio) embryos were treated with PTU by either microinjection exposure, via waterborne exposure or indirectly through bystander exposure. Melanin content, related mRNA and protein expression were examined at the end of exposure (36h post-fertilization). Direct exposure to PTU decreased the melanin content, up-regulated mRNA expressions of oculocutaneous albinism type 2 (OCA2), tyrosinase (TYR), dopachrometautomerase (DCT), tyrosinase-related protein 1 (TYRP1) and silver (SILV), and increased the protein expressions of TYR and SILV. Bystander exposure also up-regulated mRNA and protein expressions of TYR and SILV but increased melanin contents. Correlation analysis demonstrated that mRNA expressions of OCA2, TYR, DCT, TYRP1, SILV and protein expressions of TYR and SILV in bystander exposure groups were positively correlated with corresponding expressions in microinjection exposure groups. The results might have environmental implications and highlight the need to consider the bystander effects when assessing potential risks of endocrine-disrupting chemicals. [Copyright &y& Elsevier]

Abstract: Microcystin–leucine–arginine (MCLR) is the most toxic and the most commonly encountered variant of microcystins (MCs) in aquatic environment, and it has the potential for disrupting thyroid hormone homeostasis, but the molecular mechanisms underlying this process have not yet been clarified. In the present study, we observed body growth retardation associated with decreased levels of thyroid hormones (THs) in zebrafish larvae, highlighting the interferences of MCLR with the growth of fish larvae. To further our understanding of mechanisms of MCLR-induced endocrine toxicity, quantitative real-time PCR analysis was performed on hypothalamic–pituitary–thyroid (HPT) axis related genes of developing zebrafish embryos exposed to 100, 300 and 500μgL−1 MCLR until 96h post-fertilization. The expression of several genes in the HPT system, i.e., corticotropin-releasing factor (CRF), thyroid-stimulating hormone (TSH), sodium/iodide symporter (NIS), thyroglobulin (TG), thyroid receptors (TRα and TRβ) and iodothyronine deiodinases (Dio1 and Dio2) was examined using quantitatively real-time PCR. The gene expression levels of CRF, TSH, NIS and TG were significantly induced after exposure to 500μgL−1 MCLR. The transcription of TRs gene was down-regulated in a concentration-dependent manner. Up-regulation and down-regulation of Deio1 and Deio2 gene expression, respectively, were observed upon exposure to MCLR. The above results indicated that MCLR could alter gene expression in the HPT axis which might subsequently contribute to MCLR-induced thyroid disruption. [Copyright &y& Elsevier]

Cyanobacteria-derived microcystin-leucine-arginine (MCLR), commonly characterized as a hepatotoxin, has recently been found to show neurotoxicity, but the exact mechanism is still unknown. To further our understanding of the neurotoxic effects of MCLR and the mechanisms behind it, we used two-dimensional gel electrophoresis and mass spectrometry analysis to identify global protein profiles associated with MCLR-induced neurotoxicity. MCLR-treated hippocampi showed alterations in proteins involved in cytoskeleton, neurodegenerative disease, oxidative stress, apoptosis, and energy metabolism. After validation by Western blot and quantitative real-time PCR, the expressions of three proteins related to neurodegenerative disease, septin 5, α-internexin, and α-synuclein, were identified to be altered by MCLR exposure. Based on our proteomic analysis that MCLR toxicity might be linked to neurodegeneration, we examined the activity of serine/threonine-specific protein phosphatases (PPs), which are markers of neurodegenerative disease. MCLR was found to induce inhibition of PPs and abnormal hyperphosphorylation of the neuronal microtubule–associated protein tau. This was found to lead to impairment of learning and memory, accompanied by severe histological damage and neuronal apoptosis in the hippocampal CA1 regions of rats. Our results support the hypothesis that MCLR could induce neurotoxic effects, the reason for which could be attributed to the disruption of the cytoskeleton, oxidative stress, and inhibition of PPs in the hippocampus. Moreover, MCLR was found to induce tau hyperphosphorylation, spatial memory impairment, neuronal degenerative changes, and apoptosis, suggesting that this cyanotoxin may contribute to Alzheimer's disease in humans. [ABSTRACT FROM PUBLISHER]

Abstract: A solid heteropolyacid salt Ag3PW12O40 has been used as a heterogeneous catalyst for the production of 5-hydroxymethylfurfural (HMF) from fructose and glucose. The fructose was selectively dehydrated into HMF with the HMF yield as high as 77.7% and selectivity of 93.8% within 60 min at 120 °C. In addition, Ag3PW12O40 also exhibited catalytic activity for conversion of glucose into HMF. Moreover, the catalyst is tolerant to high concentration feedstock and can be recycled. The results illustrate that the Ag3PW12O40 is an excellent acid and environmentally benign solid catalyst for the production of HMF from fructose and glucose. [Copyright &y& Elsevier]

A superconducting magnet with the center field of 9.4 T is designed and fabricated for 400 MHz Nuclear Magnetic Resonance. Superconducting coil with NbTi/Cu superconducting wire is employed and cooled by re-condensed liquid helium and the magnet system with the clear-bore of 54 mm. The pulsed tube refrigerator with separated valve is employed to cool the magnet system. The superconducting magnet has an active shield with high pure copper shield to protect during quench of the shielding coil. The paper reports the electromagnetic design, and fabrication is detailed. [ABSTRACT FROM AUTHOR]

Diamond anvil cell synchrotron X-ray diffraction (XRD) experiments have been carried out on submicron-sized tungsten tetraboride (WB4) at room temperature up to 50.8 GPa with a silicone oil pressure medium. The crystal structure of WB4 remains unchanged up to the highest pressure. The isothermal bulk modulus K0 and its pressure derivative, [image omitted] , have been determined from the present compression by fitting the third-order Birch-Murnaghan equation of state: K0=325±9 GPa and [image omitted] . The high value of the bulk modulus shows that WB4 has high stiffness and/or low-compressibility. Moreover, we also found that the compression behavior of the unit cell axes (a- and c-axes) of WB4 demonstrates an anisotropic nature of compressibility. [ABSTRACT FROM AUTHOR]

Abstract: We report on the in situ electrical resistance measurements of Ti2AlC under high pressure up to 6 GPa using four-probe method in a cubic large volume press. The resistance of Ti2AlC changes smoothly with pressure without sharp anomalies, which reveals no phase transformations. The resistivity decreases with increasing pressure. At pressures above 3.5 GPa, the resistivity decreases slowly with a pressure dependence of about . In addition, the resistivity was also measured at the process of decompression. The resistivity changes slowly with a pressure dependence of about at pressures above 2.5 GPa. These results are associated with the resistivity change with temperature and could confirm that the transition metal plays the dominant role in electrical transport. [Copyright &y& Elsevier]

To investigate the apoptosis effect of SARS coronavirus nucleocapsid protein on cultured cell lines and to explore the possible pathway of apoptosis. pCDNA3.1(-)/his-myc vector containing the SARS coronavirus nucleocapsid gene (N), matric gene (M), spike gene (S) were transfected into COS-1, Huh-7 and HepG2 cells. Apoptosis induced by SARS coronavirus N protein under starvation of serum of COS-1 cells was monitored by Annexin V and electron microscopy assays. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were determined by flow cytometric assay. Cytochrome C, cleaved caspase (cysteine aspartic acid protease)-3, 9, and poly (ADP-ribose) polymerase (PARP) were detected by Western blot. After removal of serum in COS-1 cells, we observed the loss of ΔΨm, the increase of ROS and cytochrome C release into cytosol and subsequent activation of caspase-3 and PARP cleavage. The pan-caspase inhibitor z-VAD-fmk can block the activation of caspase 3, 9 and PARP cleavage. In conclusion, SARS coronavirus N protein can induce apoptosis of COS-1 cells by activating mitochondrial pathway. SARS coronavirus M, S protein can not induce apoptosis in COS-1, HepG2 and Huh-7 and SARS coronavirus N protein can not induce apoptosis in HepG2 and Huh-7 by methods used in this study. [ABSTRACT FROM AUTHOR]

The use of critical-for-life organs (e.g., liver or lung) for systemic gene therapeutics can lead to serious safety concerns. To circumvent such issues, we have considered salivary glands (SGs) as an alternative gene therapeutics target tissue. Given the high secretory abilities of SGs, we hypothesized that administration of low doses of recombinant adeno-associated virus (AAV) vectors would allow for therapeutic levels of transgene-encoded secretory proteins in the bloodstream. We administered 109 particles of an AAV vector encoding human erythropoietin (hEPO) directly to individual mouse submandibular SGs. Serum hEPO reached maximum levels 8-12 weeks after gene delivery and remained relatively stable for 54 weeks (longest time studied). Hematocrit levels were similarly increased. Moreover, these effects proved to be vector dose-dependent, and even a dosage as low as 108 particles per animal led to significant increases in hEPO and hematocrit levels. Vector DNA was detected only within the targeted SGs, and levels of AAV copies within SGs were highly correlated with serum hEPO levels (r = 0.98). These results show that SGs appear to be promising targets with potential clinical applicability for systemic gene therapeutics. [ABSTRACT FROM AUTHOR]

Clinical applications of gene transfer technology initially targeted the treatment of inherited monogenetic disorders and cancers refractory to conventional therapies. Today, gene transfer approaches are being developed for most tissues and for multiple disorders including those affecting quality of life. The focus herein is eventual application of gene transfer technology for the management of organ-directed autoimmunity. A specific example is presented: Sjögren’s syndrome and localized salivary gland gene transfer. The status of relevant pre-clinical gene transfer studies is reviewed, with an emphasis on use of adenoviral and adeno-associated viral vectors. Current limitations of effective organ-directed gene transfer are also discussed. [Copyright &y& Elsevier]

• Treatment with hMASP-2 DNA nanolipoplexes can obviously reduce the weight of hydatid cysts. • DNA nanolipoplexes of hMASP-2 could injure the germinal layers and laminated layers of hydatid cysts. • The number CD4+ T cells and CD8+ T cells were obviously increased after treatment with hMASP-2 DNA nanolipoplexes. • The frequency of PD-1+ T -cell subsets were significantly decreased after treatment with hMASP-2 DNA nanolipoplexes. • Treatment with hMASP-2 DNA nanolipoplexes could obviously accelerated the secretion of serum IFN-γ in protoscolex-infected mice. Cystic echinococcosis (CE), a complex and neglected zoonotic infectious disease, is mainly caused by larval tapeworm Echinococcus granulosus with a worldwide distribution. For CE, an effective drug treatment is not yet available. The present study was conducted to evaluate the efficacy of hMASP-2-based immunotherapy against hydatid cysts by using murine model. Eighteen weeks after infection with 2000 viable protoscoleces intraperitoneally, the infected mice were treated with hMASP-2 DNA nanolipoplexes (pcDNA3.1-hMASP-2) and albendazole respectively. After six weeks treatment, a significant reduction in the weight of cysts was observed both in the pcDNA3.1-hMASP-2 group and albendazole group compared with the untreated group (P < 0.05). The hMASP-2 DNA nanolipoplexes not only inhibited the development of germinal layer, but also induced the extensive degeneration and damage of the germinal layer cells. Furthermore, compared with the untreated group, the number of CD4+T cells and CD8+T cells and the level of serum IFN-γ were significantly increased (P < 0.05). The frequency of PD-1+ T -cell subpopulations including CD4+PD-1+T cells and CD8+PD-1+T cells and the level of serum IL-4 were notably decreased (P < 0.05) in the pcDNA3.1-hMASP-2 treatment group. Therefore, the hMASP-2 DNA nanolipoplexes displayed an effective treatment for echinococcosis through inhibiting the development of cysts and up-regulatory T-cell immunity. This new hMASP-2-based immunotherapeutic strategy could be a potential alternative for the treatment of CE, but further studies are recommended to evaluate the full potential of these hMASP-2 DNA nanolipoplexes in the treatment of human CE. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

An anvil-preformed gasket system has been developed to extend the pressure range for the widely used large volume cubic press without sacrificing the sample volume. The relationship of the sample chamber pressure versus press load for this system was calibrated at room temperature using transitions in Bi, Tl, and Ba. With similar sample volumes (8-11 mm in diameter and 8 mm in length), the anvil-preformed gasket system can generate pressures up to about 8.5 GPa, significantly higher than 6 GPa, which was generally the maximum pressure for the conventional anvil-gasket system. The details on the optimized design for the anvil-preformed gasket system are given in this note. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MCLR) was commonly regarded as a potent hepatotoxin and has been reported to cause neurotoxicity. This study was aimed to investigate how maternal MCLR exposure during pregnancy alters behavioral responses in offspring mice and the possible molecular mechanism involved in this procedure. Three doses of MCLR solutions (0, 3 or 15 μg/kg body weight) were administered subcutaneously to pregnant C57bl/6 from gestation day (GD) 6–19. Our results showed that MCLR prenatal exposure led to the impairment of learning and memory function in offspring on postnatal days (PND) 35, accompanied by endoplasmic reticulum (ER) stress and neuronal apoptosis in hippocampal CA1 regions of mice. Sixteen miRNAs in hippocampus of pups on PND 35 were significantly affected by MCLR exposure with the markedly decreased transcription of miR-181a-5p. We then found that miR-181a-5p was down-regulated, accompanied by activation of ER stress after prenatal exposure to MCLR using qPCR analysis. Furthermore, glucose-regulated protein, 78kDa/binding immunoglobulin protein (Grp78/BIP), a major ER chaperone and signaling regulator, was identified as a target of miR-181a-5p. Our study showed that miR-181a could lead to a decrease in the mRNA expression and protein levels of Grp78 by directly binding to its 3′-untranslated region (3′-UTR) in primary hippocampal neurons. Our findings indicate that the up-regulation of Grp78 mediated by inhibition of miR-181a-5p is a possible mechanism resulting in ER stress and cognitive impairment in pups following prenatal MCLR exposure. • Maternal MC-LR exposure altered behavioral responses in offspring mice. • MC-LR prenatal exposure led to endoplasmic reticulum (ER) stress and neuronal apoptosis in offspring. • Inhibition in miR-181a resulted in the activation of ER stress and subsequent apoptosis. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing neurotoxicity, but the exact mechanisms of action still remain unclear. Using proteomic analysis, forty-five proteins were identified to be significantly altered in hippocampal neurons of rats treated with MCLR. Among them, Ca2+-activated phosphatase calcineurin (CaN) and the nuclear factor of activated T-cells isoform c3 (NFATc3) were up-regulated remarkably. Validation of the changes in CaN and NFATc3 expression by Western blotting demonstrated CaN cleavage and subsequent NFATc3 nuclear translocation were generated, suggesting that exposure to MCLR leads to activation of CaN, which in turn activates NFATc3. Activation of CaN signaling has been reported to result in apoptosis via dephosphorylation of the proapoptotic Bcl-2 family member Bad. In agreement with this, our results revealed that treatment of neurons with the CaN inhibitor FK506 blocked the reduction in Bad dephosphorylation and cytochrome c (cyt c) release triggered by MCLR. Consistent with these biochemical results, we observed a marked decrease in apoptotic and necrotic cell death after MCLR exposure in the presence of FK506, supporting the hypothesis that MCLR appeared to cause neuronal toxicity by activation of CaN and the CaN-mediated mitochondrial apoptotic pathway. [ABSTRACT FROM AUTHOR]

Abstract: The high pressure and high temperature (HPHT) behavior and phase stability of titanium-aluminium carbide (Ti2AlC) were investigated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron micrograph (SEM), and energy-dispersive X-ray analysis (EDXA). The results show that the decomposition temperature of Ti2AlC decreases against pressure. At pressures of 3, 4 and 5GPa, the low temperature limits of phase segregation of the sample Ti2AlC lie between 1300 and 1200°C, 1100 and 1000°C, 900 and 800°C, respectively. The decomposition products are identified to be titanium carbide and titanium aluminium. [Copyright &y& Elsevier]