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Virulence genes expressed in Salmonella are a primary contributing factor leading to the high morbidity and mortality of salmonellosis in humans. The pathogenicity of Salmonella is mainly determined by the specific virulence factors that it carries. These factors also confer greater virulence and play a role in infection of a host and transmission of disease, and most Salmonella enterica can cause cross-infections between humans and animals. In this study, 265 samples in total were collected from a farmer’s market and two supermarkets in Xuzhou, Jiangsu province, China, including 205 pork samples and 60 chicken samples. The suspected Salmonella isolates were isolated and identified using microbiological and molecular methods, and the confirmed isolates were used for serovar analysis and antimicrobial susceptibility testing. The virulence genes of Salmonella pathogenic islands (SPIs) and Salmonella virulence plasmids (Spv) in Salmonella-positive isolates were subsequently detected. Salmonella was isolated from 29.0% of samples, and all isolates were confirmed by PCR targeting the stn gene. Among the Salmonella isolates, resistance was most frequently observed against ciprofloxacin (84.4%), followed by tetracycline (71.4%) and streptomycin (68.8%). Resistance to amoxicillin–clavulanic acid (6.3%) and aztreonam (5%) was less commonly detected. The presence of the following virulence genes was determined by specific PCRs: hilA (SPI-1), sifA (SPI-2), misL (SPI-3), siiE (SPI-4), sopB (SPI-5), and spvC. The detection rate for SPI-1 to SPI-5 was 93.5, 87.0, 97.4, 97.4, and 97.4%, respectively. In addition, the detection rate of the spvC gene was 96.1%. Except for sopB (94.7%), all isolates of the dominant serovar S. enterica subsp.. enterica serovar Enteritidis contained all virulence genes from SPI-1 to SPI-5. This study demonstrated the epidemiological status of Salmonella in raw meat products in Xuzhou, and the complex antibiotic resistance and high isolation rate of virulence genes observed reveal many potential risks of which the findings presented herein will provide orientation to improve public health safeguards. [ABSTRACT FROM AUTHOR]

SC9-2 is a recombinant Marek’s disease virus (MDV) strain lacking the meq oncogene. Previous study demonstrated that SC9-2 virus provides good protection against challenge with a very virulent MDV rMd5, but it induces immunosuppressive effects in specific pathogen-free (SPF) chickens. In the present study, SC9-2 was serially passaged on chicken embryo fibroblast (CEF) cell cultures. The pathogenicity and immune efficacy of SC9-2/10th and SC9-2/40th against rMd5 were evaluated. Animal experimental results showed that SC9-2/10th and SC9-2/40th showed no lethality or tumorigenicity in SPF chickens. Body weight of chickens inoculated with SC9-2/40th were significantly higher than that of the chickens inoculated with SC9-2/10th but lower than that of the uninoculated controls. The severity of bursa and thymus atrophy (BTA) and spleen enlargement in SC9-2/40th-inoculated chickens were also weaker than the SC9-2/10th-inoculated ones but stronger than the uninoculated controls. Chickens inoculated with SC9-2/40th and SC9-2/10th showed similar antibody levels induced by H9N2 subtype avian influenza virus/Newcastle disease virus inactivated vaccines, both of which were lower than the uninoculated controls. Replication of SC9-2/40th was significantly lower than SC9-2/10th in feather follicle epithelium (FFE) of infected chickens. The immune protection index of SC9-2/40th was also lower than that of SC9-2/10th, but the difference was not significantly, and both of which were significant higher than that of the commercial MDV vaccine CVI988/Rispens. The results of our studies demonstrated that SC9-2/40th showed weaker severity of BTA, spleen enlargement, and body weight loss and lower replication level in FFE than SC9-2/10th in SPF chickens. However, SC9-2/40th was able to confer better immune protection as compared with CVI988/Rispens vaccination in SPF chickens. In conclusion, serially attenuation of SC9-2 in CEFs reduced the lymphoid organ atrophy and replication in SPF chickens, and the immune protective efficacy of attenuated viruses was still superior than CVI988/Rispens. [ABSTRACT FROM AUTHOR]

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (Vmem) and quiescence. We found that Vmem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas Vmem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high Vmem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and upregulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and Vmem in the Artemia model. [ABSTRACT FROM AUTHOR]

A novel host material, namely 9-(6-(3-phenyl-5-(pyridin-2-yl)-4H-1,2,4-triazol-4-yl)hexyl)-9H-carbazole (PPHCZ) was designed and synthesized by incorporating 1, 2, 4-triazol as the electron-withdrawing moiety and carbazole as electron-donating moiety using hexyl as bridge. The photophysical, electrochemical, thermal properties and performances in phosphorescent organic light-emitting devices (PhOLED) were thoroughly characterized. PPHCZ with a high triplet energy level (3.01 eV) exhibited an obvious intermolecular interaction in thin film. Green and blue PhOLEDs using fac-tris(2-phenylpyridine)iridium and iridium(III) bis(4,6-difluorophenyl)-pyridinato N,C²']picolinate as phosphorescent dopants have been fabricated. [ABSTRACT FROM AUTHOR]

Aim: To derive a more precise estimation of carotid intima-media thickness (CIMT) levels in patients with type 1 diabetes mellitus (T1DM) by meta-analysis. Methods: PubMed and Embase databases were searched to identify all available studies comparing CIMT levels between T1DM group and control group. Meta-analysis was performed to compare the difference of overall mean CIMT levels between the two groups. Publication bias was evaluated by funnel plot, Begg' test and Egger' test. Meta-regression analysis was conducted to investigate the influential factors on CIMT difference. The meta-analysis was conducted by STATA 12.0 software. Results: A total of 1840 articles were obtained after searching databases; 47 studies were finally included in the meta-analysis. Significant heterogeneity was observed among these studies (Q = 768.75, < 0.001, I² = 94.0%). Compared with the control group, the T1DM group had significantly higher CIMT levels (standardized mean difference: 1.01, 95% CI: 0.75-1.28; < 0.001). A likely source of heterogeneity was Newcastle-Ottawa Scale (NOS) scores and sample size ratio of patents and controls. The funnel plot did not show a skewed or asymmetrical shape, and the result of Begg' test and Egger' test was P = 0.178 and P = 0.145 respectively. Accordingly, it could be assumed that publication bias was not present. Conclusion: T1DM patients have significantly increased CIMT levels compared to control subjects. [ABSTRACT FROM AUTHOR]

High performance nanofiltration (NF) membranes for heavy metal removal have been molecularly designed by adsorption of chelating polymers containing negatively charged functional groups such as poly (acrylic acid-co-maleic acid) (PAM), poly (acrylic acid) (PAA) and poly (dimethylamine-co-epichlorohydrin-co-ethylenediamine) (PDMED) on the positively charged polyethyleneimine (PEI) cross-linked P84 hollow fiber substrates. Not only do these chelating polymers change the membrane surface charge and pore size, but also provide an extra mean to remove heavy metal ions through adsorption in addition to traditional steric effect and Donnan exclusion. The adsorbed membranes have comparable water permeability and superior rejections to heavy metals, for instance, Pb(NO3)2, CuSO4, NiCl2, CdCl2, ZnCl2, Na2Cr2O7 and Na2HAsO4, with rejections higher than 98%. The membranes also display excellent rejections to mixed ions with rejections more than 99%. The newly developed membranes show reasonably stability during 60-h tests as well as multiple washes. [ABSTRACT FROM AUTHOR]

Eleutheronema tetradactylum is an economically important fish species in China water. To investigate the genetic diversity and describe population structure of it, an 1151 base pair (bp) fragment of the mitochondrial DNA Cytb sequence was analyzed in 120 individuals from four populations in the East China Sea and the South China Sea. A total of 16 haplotypes were defined by 24 variable nucleotide sites. High level of haplotype diversity and low nucleotide diversity were observed in all populations. The results of AMOVA detected that 89.44% of the genetic variation occurred within populations. Significant genetic differentiations were detected among populations (0.05097, P < 0.05), but no large-scale regional differences were detected. Analysis of neutral evolution and mismatch distribution suggested no recent population expansion happened. The present results provided new information for genetic assessment, fishery management and conservation of this species. [ABSTRACT FROM AUTHOR]

The concept of "biased agonism" arises from the recognition that the ability of an agonist to induce a receptor-mediated response (i.e. "efficacy") can differ across the multiple signal transduction pathways (e.g. G protein and β-arrestin (βarr)) emanating from a single GPCR. Despite the therapeutic promise of biased agonism, the molecular mechanism(s) whereby biased agonists selectively engage signaling pathways remain elusive. This is due in large part to the challenges associated with quantifying ligand efficacy in cells. To address this, we developed a cell-free approach to directly quantify the transducer-specific molecular efficacies of balanced and biased ligands for the angiotensin II type 1 receptor (AT1R), a prototypic GPCR. Specifically, we defined efficacy in allosteric terms, equating shifts in ligand affinity (i.e. KLo/KHi) at AT1R-Gq and AT1R-βarr2 fusion proteins with their respective molecular efficacies for activating Gq βarr2. Consistent with ternary complex model predictions, transducer-specific molecular efficacies were strongly correlated with cellular efficacies for activating Gq βarr2. Subsequent comparisons across transducers revealed that biased AT1R agonists possess biased molecular efficacies that were in strong agreement with the signaling bias observed in cellular assays. These findings not only represent the first measurements of the thermodynamic driving forces underlying differences in ligand efficacy between transducers but also support a molecular mechanism whereby divergent transducer-specific molecular efficacies generate biased agonism at a GPCR. [ABSTRACT FROM AUTHOR]

Early-stage subglottic lesions are easily misdiagnosed as bronchial asthma. We report on 4 cases of rare subglottic lesions. Our aim is to provide insights for the accurate diagnosis of subglottic lesions. Four cases of subglottic lesions with bronchial asthma as the initial symptom were studied retrospectively. The lesions were a mixed tumor, a mucoepidermoid carcinoma, laryngeal amyloidosis, and relapsing chondritis. All of the patients had received standard but ineffective antiasthma treatment when their tumors were in the early stage. Each patient underwent a tracheotomy because of a laryngeal obstruction. Each patient was treated properly and in a timely manner after the primary disease had been diagnosed, and the tracheal cannula was removed; however, 1 patient survived with a tracheal cannula in place. We must be aware of the risk of ineffective treatment because subglottic lesions may be misdiagnosed as bronchial asthma. The accurate diagnosis and timely treatment of the primary disease are critical to a good prognosis. [ABSTRACT FROM AUTHOR]

The widespread occurrence of pharmaceutically active compounds (PhACs) in the environment has prompted great concern due to their potential impacts on wildlife and humans. The degradation of two of the most commonly detected PhACs, carbamazepine (CBZ) and ibuprofen (IBP), was investigated by a nano-magnetite (Fe3O4) heterogeneous Fenton-like reaction in aqueous suspensions of nano-Fe3O4 in the absence and presence of montmorillonite clay. Experimental design and response surface methodology (RSM) were applied to evaluate the effects of important factors. The results showed that hydroxyl radical (·OH) formation by the heterogeneous decomposition of H2O2 on the Fe3O4 nanoparticle surface (·OHss) plays the dominant role in CBZ and IBP degradation at neutral pH. The degradation of CBZ and IBP followed pseudo-first-order kinetics, and the degradation rate constants (k) in aqueous suspensions were 0.182 and 0.121 h−1, respectively. In addition, significant adsorption of CBZ to the montmorillonite clay occurs at neutral pH, while IBP is not adsorbed, due to electrostatic repulsion. As a result, an inhibition effect of adsorption on the degradation of CBZ (kCBZ = 0.127 h−1) in clay slurry was observed, but not for IBP degradation (kIBP = 0.202 h−1). The major intermediates, identified by solid phase extraction (SPE) followed LC–MS analysis, included hydroxy-CBZs, dihydroxy-CBZs, CBZ-10,11-diol, and hydroxy-CBZ-10,11-diols in CBZ degradation; and hydroxy-IBPs, dihydroxy-IBPs, trihydroxy-IBPs, tetrahydroxy-IBPs, 4-isobutylacetophenone and 1-(4-isobutylphenyl)ethanol in IBP degradation. The possible pathways of CBZ and IBP degradation were proposed based on the identified intermediates. [Copyright &y& Elsevier]

Abstract: This paper researches on the combination between wavelet transformation and neural network to realize the transient power quality disturbance signals’ recognition. Firstly, the mathematical models of five kinds of transient disturbance signals, such as voltage surging, voltage sag, voltage interruption, transient pulse and transient oscillation are founded. Then, using the nice time-frequency characteristic of wavelet, the sample signal''s feature vectors are extracted. At last these feature vectors are input into BP neural network. Using the nice self-learning ability the disturbance signals can be classified and recognized. The examples show that the method has a higher discrimination. It''s effective to resolve transient power quality problem. [Copyright &y& Elsevier]

Heterogeneous Fenton-like reactions on nano-magnetite (Fe3O4) were investigated for the degradation of p-Nitrophenol (p-NP). A four factor central composite design (CCD) coupled with response surface methodology (RSM) was applied to evaluate and optimize the important variables. A significant quadratic model (P-value < 0.0001, R2=0.9442) was derived using analysis of variance (ANOVA), which was adequate to perform the process variables optimization. Optimum conditions were determined to be 1.5gL−1 Fe3O4, 620 mM H2O2, pH 7.0 and 25–45 mg L−1 p-NP. More than 90% of p-NP was experimentally degraded after 10 h of reaction time under the optimum conditions, which agreed well with the model predictions. The results demonstrated that the degradation of p-NP was due to the attack of hydroxyl radicals (OH) generated by the surface-catalyzed decomposition of hydrogen peroxide on the nano-Fe3O4, i.e. heterogeneous Fenton-like reactions. Possible mechanisms of p-NP degradation in this system were proposed, based on intermediates identified by LC–MS and GC–MS and included benzoquinone, hydroquinone, 1,2,4-trihydroxybenzene and p-nitrocatechol. The kinetic analysis implied that the generation rate of ·OH (V·OH) was increased along with the degradation of p-NP. This was attributed to the formation of acidic products, which decreased the solution pH and enhanced the decomposition of absorbed hydrogen peroxide via a radical producing pathway on the nano-Fe3O4 surface. [ABSTRACT FROM AUTHOR]

ROMK1 channels are located in the apical membrane of the connecting tubule and cortical collecting duct and mediate the potassium secretion during normal dietary intake. We used a perforated whole-cell patch clamp to explore the effect of angiotensin II on these channels in HEK293 cells transfected with green fluorescent protein (GFP)-ROMK1. Angiotensin II inhibited ROMK1 channels in a dose-dependent manner, an effect abolished by losartan or by inhibition of protein kinase C. Furthermore, angiotensin II stimulated a protein kinase C-sensitive phosphorylation of tyrosine 416 within c-Src. Inhibition of protein tyrosine kinase attenuated the effect of angiotensin II. Western blot studies suggested that angiotensin II inhibited ROMK1 channels by enhancing its tyrosine phosphorylation, a notion supported by angiotensin II's failure to inhibit potassium channels in cells transfected with the ROMK1 tyrosine mutant (R1Y337A). However, angiotensin II restored the with-no-lysine kinase-4 (WNK4)-induced inhibition of R1Y337A in the presence of serum-glucocorticoids-induced kinase 1 (SGK1), which reversed the inhibitory effect of WNK4 on ROMK1. Moreover, protein tyrosine kinase inhibition abolished the angiotensin II-induced restoration of WNK4-mediated inhibition of ROMK1. Angiotensin II inhibited ROMK channels in the cortical collecting duct of rats on a low sodium diet, an effect blocked by protein tyrosine kinase inhibition. Thus, angiotensin II inhibits ROMK channels by two mechanisms: increasing tyrosine phosphorylation of the channel and synergizing the WNK4-induced inhibition. Hence, angiotensin II may have an important role in suppressing potassium secretion during volume depletion. [ABSTRACT FROM AUTHOR]

GRIM-19 (Gene associated with Retinoid-IFN-induced Mortality-19) was originally isolated as a growth suppressor in a genome-wide knockdown screen with antisense libraries. Like classical tumor suppressors, mutations, and/or loss of GRIM-19 expression occur in primary human tumors; and it is inactivated by viral gene products. Our search for potential GRIM-19-binding proteins, using mass spectrometry, that permit its antitumor actions led to the inhibitor of cyclin-dependent kinase 4, CDKN2A. The GRIM-19/CDKN2A synergistically suppressed cell cycle progression via inhibiting E2F1-driven gene expression. The N terminus of G RIM-19 and the fourth ankyrin repeat of CDKN2A are crucial for their interaction. The biological relevance of these interactions is underscored by observations that GRIM-19 promotes the inhibitory effect of CDKN2A on CDK4; and mutations from primary tumors disrupt its ability to interact with GRIM-19 and suppress E2F1-driven gene expression. [ABSTRACT FROM AUTHOR]

The phosphatase of regenerating liver (PRL) phosphatases are implicated in a number of tumorigenesis and metastasis processes. The PRLs are unique among protein-tyrosine phosphatases in that they have extremely low phosphatase activity, a high propensity for trimer formation, and a polybasic region that precedes the C-terminal prenylation motif. To investigate the functional significance of these distinctive biochemical and structural features, we established a cell-based system in which ectopic PRL1 expression increased cell proliferation and migration, whereas knockdown of endogenous PRL1 abrogated these cellular activities. We showed that the intrinsic PRL1 phosphatase activity is obligatory for its biological function. We provided evidence that trimerization may be a general property for all PRL enzymes, and that PRL1 trimer formation is essential for the PRL1-mediated cell growth and migration. This finding indicates a novel mechanism for phosphatase regulation. We further demonstrated that the conserved C-terminal polybasic region is important for specific phosphoinositide recognition by PRL1. Both the polybasic residues and the adjacent prenylation motif are required for proper PRL1 subcellular localization and full biological activity. [ABSTRACT FROM AUTHOR]

Abstract: Accumulated evidence have shown that a series of morphological alternations occur in patients with epilepsy and in different epileptic animal models. Given most of animal model studies have been focused on adulthood stage, the effect of recurrent seizures to immature brain in neonatal period has not been well established. This study was designed to observe the certain morphological changes following recurrent seizures occurred in the neonatal rats. For seizure induction, neonatal Wistar rats were intraperitoneally injected with pilocarpine on postnatal day 1 (P1), P4 and P7. Rat pups were grouped and sacrificed at 1d, 7d, 14d and 42d after the last pilocarpine injection respectively. Bromodeoxyuridine (BrdU) was intraperitoneally administered 36h before the rats were sacrificed. BrdU single and double labeling with neuronal markers were used to analyze cell proliferation and differentiation. Nissl and Timm staining were performed to evaluate cell loss and mossy fiber sprouting. Rats with neonatal seizures had a significant reduction in the number of Bromodeoxyuridine-(BrdU) labeled cells in the dentate gyrus compared with the control groups when the animals were killed either 1 or 7 days after the third seizure (P <0.05) but there was no difference between two groups on P21. On the contrary, BrdU-labeled cells significantly increased in the experimental group compared with control group on P49 (P <0.05). The majority of the BrdU-labeled cells colocalized with neuronal marker-NF200 (Neurofilament-200). Nissl staining showed that there was no obvious neuronal loss after seizure induction over all different time points. Rats with the survival time of 42 days after neonatal seizures developed to increased mossy fiber sprouting in both the CA3 region and supragranular zone of the dentate gyrus compared with the control groups (P <0.05). Taken together, the present findings suggest that synaptic reorganization only occurs at the later time point following recurrent seizures in neonatal rats, and neonatal recurrent seizures can modulate neurogenesis oppositely over different time window with a down-regulation at early time and up-regulation afterwards. [Copyright &y& Elsevier]

Annexin II has been implicated in membrane fusion during the exocytosis of lamellar bodies from alveolar epithelial type II cells. Most previous studies were based on the fusion assays by using model membranes. In the present study, we investigated annexin II-mediated membrane fusion by using isolated lamellar bodies and plasma membrane as determined by the relief of octadecyl rhodamine B (R18) self-quenching. Immunodepletion of annexin II from type II cell cytosol reduced its fusion activity. Purified annexin II tetramer (AIIt) induced the fusion of lamellar bodies with the plasma membrane in a dose-dependent manner. This fusion is Ca[sup 2+]-dependent and is highly specific to Alit because other annexins (I and II monomer, III, IV, V, and VI) were unable to induce the fusion. Modification of the different functional residues of Alit by N-ethylmaleimide, nitric oxide, or peroxynitrite abolished AIIt-mediated fusion. Arachidonic acid enhanced AIIt-mediated fusion and reduced its Ca[sup 2+] requirement to an intracellularly achievable level. This effect is due to membrane-bound arachidonic acid, not free arachidonic acid. Other fatty acids including linolenic acid, palmitoleic acid, myristoleic acid, stearic acid, palmitic acid, and myristic acid had little effect. AIIt-mediated fusion was suppressed by the removal of arachidonic acid from lamellar body and plasma membrane using bovine serum albumin. The addition of arachidonic acid back to the arachidonic acid-depleted membranes restored its fusion activity. Our results suggest that the fusion between lamellar bodies with the plasma membrane is driven by the synergistic action of AIIt and arachidonic acid. [ABSTRACT FROM AUTHOR]

The pathogenic bacteria Yersinia are causative agents in human diseases ranging from gastrointestinal syndromes to bubonic plague. There is increasing risk of misuse of infectious agents, such as Yersinia pestis, as weapons of terror as well as instruments of warfare for mass destruction. Because the phosphatase activity of the Yersinia protein tyrosine phosphatase, YopH, is essential for virulence in the Yersinia pathogen, potent and selective YopH inhibitors are expected to serve as novel anti-plague agents. We have identified a specific YopH small molecule inhibitor, p-nitrocatechol sulfate (pNCS), which exhibits a K[sub i] value of 25 µM for YopH and displays a 13-60-fold selectivity in favor of YopH against a panel of mammalian PTPs. To facilitate the understanding of the underlying molecular basis for tight binding and specificity, we have determined the crystal structure of YopH in complex with pNCS at a 2.0-Å resolution. The structural data are corroborated by results from kinetic analyses of the interactions of YopH and its site-directed mutants with pNCS. The results show that while the interactions of the sulfuryl moiety and the phenyl ring with the YopH active site contribute to pNCS binding affinity, additional interactions of the hydroxyl and nitro groups in pNCS with Asp-356, Gln-357, Arg-404, and Gln-446 are responsible for the increased potency and selectivity. In particular, we note that residues Arg-404, Glu-290, Asp-356, and a bound water (WAT185) participate in a unique H-bonding network with the hydroxyl group ortho to the sulfuryl moiety, which may be exploited to design more potent and specific YopH inhibitors. [ABSTRACT FROM AUTHOR]

Examines the crystal structure of protein-tyrosine phosphatase 1B (PTP1B) complexed with a potent and selective bidentate inhibitor. Crystallization and crystal packing; Overall structure of PTP1B-2 complex; Interactions between compound 2 and PTP1B beyond the active site; Mutational analysis of the interactions between PTP1B and its inhibitors.

Focuses on the association of small guanosine triphosphatase (GTPase) Rah/Rab34 with membrane ruffles and macropinosomes. Promotion of macropinosome formation; Exhibition of extremely low GTPase activity in vitro of wild-type Rah; Presence of Rab5 in endosomes at later stages; Facilitation of the formation of macropinosomes by the treatment of platelet-derived growth factor by Rah.

Highlights • Disintegration of the sludge flocs by Fenton, neutralization and agregation of EPS by Moringa oleifera are the conditioners mechanisms. • The reduction of the water content by Fenton and the increase of the particle size by Moringa oleifera improving sludge dewaterability. • The combination of Fenton with Moringa oleifera is an interesting perspective for sludge dewaterability. Abstract The specific resistance to filtration (SRF), sludge cake water content, bound water content, extracellular polymeric substances (EPS) content, particle size, and microstructure of the flocs were measured to evaluate the efficiency of the combined treatment of Moringa oleifera (MO) with Fenton for sludge dewaterability. Results showed that the water content of the sludge cake was reduced from 73.86 to 62% when the dosages of Fe2+, H 2 O 2 , and MO were 31.93, 22.87, and 800 mg/g TS, respectively. The Fenton- Moringa conditioned sludge (FMCS) presented a better dewaterability than that derived from the solo application of MO or Fenton, with the SRF closely correlating with the EPS central liquor (CL-EPS; R2 = 0.62), the light bound EPS (LB-EPS; R2 = 0.55) and the tight bound EPS (TB-EPS;R2= -0.83). Moreover, the protein content of LB-EPS and TB-EPS in conditioned sludge showed a strong positive correlation with SRF (R2= -0.79 with LB-EPS and R2 = 0.91 with TB-EPS). The zeta potential further displayed a strong correlation with SRF (R2 = 0.83). Under Fenton- Moringa conditioning, the particle size of the sludge did not show a significant correlation with SRF (R2=-0.20); however, there was a significant correlation between the particle size and the zeta potential (R2 = 0.56). The observed particle size was larger than that of Fenton conditioned sludge, allowing a better settling of the sludge particles. Furthermore, the microstructure of the FMCS also showed a more porous structure. While Fenton reduces the water content in sludge by disintegrating flocs, MO increases the particle size, neutralizes and aggregates the EPS, hence improving sludge dewaterability and rendering Fenton- MO attractive for sludge treatment. [ABSTRACT FROM AUTHOR]

An abstract of the article "Assays for Functional Properties of Rab34 in Macropinosome Formation," by Peng Sun and Takeshi Endo is presented.

Marek's disease (MD) has become increasingly common in China, resulting in considerable economic loss. The etiological agent is unclear. In this study, we isolated a field MD virus (MDV) strain, designated SX1301, from CVI988/Rispens-vaccinated chickens with tumors. Co-infection of avian leukosis virus, reticuloendotheliosis virus, and chicken infectious anemia virus was excluded by polymerase chain reaction, enzyme-linked immunosorbant assay, DNA blotting hybridization, and indirect immunofluorescence assay. As with most strains isolated in China, SX1301 had the same amino acid mutation of meq protein at positions 77E, 80Y, and 115A. Animal experimental results showed development of lethal MD in 57% and MD tumor in 23% of the specific pathogen-free chickens inoculated with SX1301, with tumors mainly distributed in spleen, liver, and kidney. CVI988/Rispens protected 83% of chickens upon challenge with SX1301, with a mortality rate and tumor incidence of 10% and 7%, respectively. These results implicated SX1301 as a virulent MDV strain, with commercial MDV vaccine CVI988/Rispens unable to confer adequate protection against SX1301. There have been no reports of very virulent (vv) plus MDV in China, but frequently occurring virulent MDV may account for the repeated outbreaks of MD. Vaccines with greater efficacy are needed to protect against MDV. [ABSTRACT FROM AUTHOR]

Jumonji domain-containing 3 (JMJD3/KDM6B) is a histone demethylase that plays an important role in regulating development, differentiation, immunity, and tumorigenesis. However, the mechanisms responsible for the epigenetic regulation of inflammation during mastitis remain incompletely understood. Here, we aimed to investigate the role of JMJD3 in the lipopolysaccharide (LPS)-induced mastitis model. GSK-J1, a small molecule inhibitor of JMJD3, was applied to treat LPSinduced mastitis in mice and in mouse mammary epithelial cells in vivo and in vitro. Breast tissues were then collected for histopathology and protein/gene expression examination, and mouse mammary epithelial cells were used to investigate the mechanism of regulation of the inflammatory response. We found that the JMJD3 gene and protein expression were upregulated in injured mammary glands during mastitis. Unexpectedly, we also found JMJD3 inhibition by GSK-J1 significantly alleviated the severity of inflammation in LPS-induced mastitis. These results are in agreement with the finding that GSK-J1 treatment led to the recruitment of histone 3 lysine 27 trimethylation (H3K27me3), an inhibitory chromatin mark, in vitro. Furthermore, mechanistic investigation suggested that GSK-J1 treatment directly interfered with the transcription of inflammatory-related genes by H3K27me3 modification of their promoters. Meanwhile, we also demonstrated that JMJD3 depletion or inhibition by GSK-J1 decreased the expression of toll-like receptor 4 and negated downstream NF-κB proinflammatory signaling and subsequently reduced LPSstimulated upregulation of Tnfa, Il1b, and Il6. Together, we propose that targeting JMJD3 has therapeutic potential for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

This paper considers a new type of optimization problems, the optimal standby mode selection problem in 1-out-of- N : G warm standby systems where multiple standby mode choices are available to provide different levels of operation readiness of standby elements and further to achieve a balance between fast restoration and low operation cost. Given the desired redundancy level and a fixed set of standby mode choices, the objective of the optimal system design is to choose a standby mode for each of redundant elements so as to minimize expected mission cost of the system subject to a certain reliability constraint. An iterative procedure is first suggested to evaluate system reliability and expected mission cost simultaneously. Based on the suggested evaluation algorithm, a genetic algorithm is then used as an optimization tool for solving the formulated optimal standby mode selection problem in 1-out-of- N : G warm standby systems. Examples are given to illustrate the considered evaluation and optimization problems as well as the proposed solution methodology. [ABSTRACT FROM AUTHOR]

We report an innovative development of novel double layered photoanodes made of hierarchical TiO2 micro-corollas as the overlayer and TiO2 nanoforest as the underlayer (HTCF), for dye-sensitized solar cells (DSSCs). They are obtained by a facile hydrothermal reaction of TiO2 nanorods array with top microspheres (MS)/FTO (Fluorine-doped tin oxide) glass substrate in an alkaline solution. In this process, the microspheres and nanorods are transformed into micro-corollas and nanotrees, respectively. The photoanodes with HTCF structure can greatly improve the light scattering ability due to their novel structures. Moreover, the enhanced surface area of HTCF can lead to larger dye loading, which achieves the higher light harvesting capacity. Base on the fast electron transport of the interior nanorods, higher light scattering and harvesting capacities, this novel HTCF photoanode realizes tri-functions. The overall power conversion efficiency (PCE) of the HTCF DSSCs are 51% increase in the conversion efficiency compare with those of constructed by bare TiO2 nanorod arrays. In our work, tri-functions of photoanodes are obtained by improving the 1D TiO2 nanostructures (nanorod, nanowire, nanotube et al.). To the best of our knowledge, it is a significant fabrication technology breakthrough for the photoanode of dye-sensitized solar cells. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) signaling through its receptor, TrkB, modulates survival, differentiation, and synaptlc activity of neurons. Both full-length TrkB (TrkB-FL) and its isoform T1 (TrkB.T1) receptors are expressed in neurons; however, whether they follow the same endocytic pathway after BDNF treatment is not known. In this study we report that TrkB-FL and TrkB.T1 receptors traverse divergent endocytic pathways after binding to BDNF. We provide evidence that in neurons TrkB.T1 receptors predominantly recycle back to the cell surface by a "default" mechanism. However, endocytosed TrkB-FL receptors recycle to a lesser extent in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner which relies on its tyrosine kinase activity. The distinct role of Firs in promoting recycling of internalized TrkB-FL receptors is independent of its ubiquitin-interacting motif. Moreover, Hrs-sensitive TrkB-FL recycling plays a role in BDNF-induced prolonged mitogen-activated protein kinase (MAPK) activation. These observations provide evidence for differential postendocytic sorting of TrkB-FL and TrkB.T1 receptors to alternate intracellular pathways. [ABSTRACT FROM AUTHOR]

Pheromone receptors (PRs) recognize specific pheromone compounds to guide the behavioral outputs of insects, which are the most diverse group of animals on earth. The activation of PRs is known to couple to the calcium permeability of their coreceptor (Orco) or putatively with G proteins; however, the underlying mechanisms of this process are not yet fully un-derstood. Moreover, whether this transverse seven trans-membrane domain (7TM)-containing receptor is able to couple to arrestin, a common effector for many conventional 7TM receptors, is unknown. Herein, using the PR BmOR3 from the silk moth Bombyx mori and its coreceptor BmOrco as a template, we revealed that an agonist-induced conformational change of BmOR3 was transmitted to BmOrco through transmembrane segment 7 from both receptors, resulting in the activation of BmOrco. Key interactions, including an ionic lock and a hydrophobic zipper, are essential in mediating the functional coupling between BmOR3 and BmOrco. BmOR3 also selectively coupled with Gi proteins, which was dispensable for BmOrco coupling. Moreover, we demonstrated that trans-7TM BmOR3 recruited arrestin in an agonist-dependent manner, which indicates an important role for BmOR3-BmOrco complex formation in ionotropic functions. Collectively, our study identified the coupling of G protein and arrestin to a prototype trans-7TM PR, BmOR3, and provided important mechanistic insights into the coupling of active PRs to their downstream effectors, including coreceptors, G proteins, and arrestin. [ABSTRACT FROM AUTHOR]

The adhesion GPCR ADGRG2, also known as GPR64, is a critical regulator of male fertility that maintains ion/pH homeostasis and CFTR coupling. The molecular basis of ADGRG2 function is poorly understood, in part because no endogenous ligands for ADGRG2 have been reported, thus limiting the tools available to interrogate ADGRG2 activity. It has been shown that ADGRG2 can be activated by a peptide, termed p15, derived from its own N-terminal region known as the Stachel sequence. However, the low affinity of p15 limits its utility for ADGRG2 characterization. In the current study, we used alanine scanning mutagenesis to examine the critical residues responsible for p15-induced ADGRG2 activity. We next designed systematic strategies to optimize the peptide agonist of ADGRG2, using natural and unnatural amino acid substitutions. We obtained an optimized ADGRG2 Stachel peptide T1V/F3Phe(4-Me) (VPM-p15) that activated ADGRG2 with significantly improved (>2 orders of magnitude) affinity. We then characterized the residues in ADGRG2 that were important for ADGRG2 activation in response to VPM-p15 engagement, finding that the toggle switch W6.53 and residues of the ECL2 region of ADGRG2 are key determinants for VPM-p15 interactions and VPM-p15-induced Gs or arrestin signaling. Our study not only provides a useful tool to investigate the function of ADGRG2 but also offers new insights to guide further optimization of Stachel peptides to activate adhesion GPCR members. [ABSTRACT FROM AUTHOR]

The sustainability paradigm has gained global attention, and the same has been expected from the economies having increasing levels of environmental footprints over the past couple of decades. This research aims to investigate the nexus between clean energy technologies and climate change mitigation among the top ecologically pollutant (TEP) economies during 1996–2020. The research incorporated other drivers of climate change, including energy efficiency, industrialization, and sustainable policies through environmental regulations. The methodological context covers the necessary preliminary tests and the Method of Moment Quantile Regression (MMQR). The preliminary results indicate that TEP economies are interdependent with the heterogenous slope coefficients, stationarity data trends, and cointegrated relationships. The findings from the MMQR unveiled that clean energy technologies tend to mitigate climate change from 0.10th to 0.70th quantiles. Relatedly, energy efficiency reduces the environmental burden across all the quantiles except for the 0.10th one. Conversely, industrialization and economic growth cause an upward shift in climate change among TEP economies across all the quantiles, suggesting a need to shift production-based economies to more service-intensive ones. However, the study found no significant evidence for the nexus between sustainable environmental policies and climate change. The robustness checks also validate the MMQR estimations; however, their parameters' magnitude substantially varied. These outcomes encourage policymakers to implement holistic strategies supporting energy innovation, technologies, and efficiency improvements while controlling the adverse effects of industrialization and traditional growth models. [Display omitted] • Mitigating climate change needs a universal call. • A novel approach, MMQR, has been applied. • Both clean energy technologies and energy efficiency reduce ecological footprints. • Industrialization and economic growth disturb the sustainability paradigm. [ABSTRACT FROM AUTHOR]

Two novel bipolar Ir(III) complexes named (Czppy) 2 Ir(tfmptz) and (Czppy) 2 Ir(pptz) were synthesized and characterized, where the Czppy is 9-(4-(pyridin-2-yl)phenyl)-9H-carbazole, tfmptz refers to 2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)pyridine and Hpptz represents 2-(1H-tetrazol-5-yl)pyridine, respectively. Their molecular structures were confirmed by 1 H NMR and photophysical were investigated. The performances in phosphorescent organic light emitting devices (PhOLEDs) were characterized by a heavy doping concentration of 20 wt% in host as emitting layer. The results suggest that the number of nitrogen atoms in ancillary has no obvious effects on their photophysical properties. Both (Czppy) 2 Ir(tfmptz) and (Czppy) 2 Ir(pptz) display the blue-green emission with the peaks at 492, 526 nm. The performances of complexes (Czppy) 2 Ir(tfmptz) in PhOLEDs superior to that of the (Czppy) 2 Ir(pptz) due to the poor thermal stability. [ABSTRACT FROM AUTHOR]

The diagnosis of avian leukosis virus subgroup J (ALV-J) infection in Chinese Partridge Shank chickens was confirmed by necropsy, histopathological examinations, antibody tests, viral isolation, immunofluorescence assays, and sequence analysis. Myelocytoma, myeloma, and fibrosarcoma were simultaneously found in Partridge Shank flock with ALV-J infection. Sequence analysis of the env genes of ALVJ demonstrated that both gp85 and gp37 were highly homologous among the three strains from local chickens of those among ALV-J strains isolated from white meat-type chickens. The phylogenetic trees indicated that the three strains isolated in this study were closely related to reference strains isolated in so-called Chinese yellow chickens and some strains isolated from white meat-type chickens, both from the USA and China. The observed ALV-J infection was the first report on Partridge Shank chickens, and myelocytoma, myeloma, and fibrosarcoma were found at the same time in this batch of local chickens. [ABSTRACT FROM AUTHOR]

Objective To observe the change in plasma gelsolin levels among burn patients, and explore its impact on patient prognosis. Methods This prospective cohort study includes 98 burn patients with burns ≥30% TBSA, who were admitted to our institution between January 2010 and June 2013. Patients were grouped according to burn sizes, development and severity of sepsis, and survival from sepsis. The plasma gelsolin levels among different groups were compared by repeated measure ANOVA. The relationship between plasma gelsolin levels and the presence of sepsis and prognosis was examined by logistic regression. Results The plasma gelsolin levels decreased with increasing burn sizes and increasing sepsis severity, with the lowest gelsolin level observed at 7 days after the burn. The plasma gelsolin concentrations were significantly lower among patients with sepsis than those without ( P < 0.001), and were lower among those who died after sepsis than those who survived ( P < 0.001). Logistic regression suggested that plasma gelsolin level was inversely associated with the occurrence of sepsis [ OR 0.873 (95% CI 0.693–0.993)] and survival after sepsis [ OR 0.939 (95% CI 0.859–0.992)]. Discussion Plasma gelsolin levels decrease after burn. The level is significantly lower among those with large burns and those with combined sepsis. Plasma gelsolin levels can be used to predict the prognosis of burn patients. [ABSTRACT FROM AUTHOR]

In order to investigate the relationship between the PD-1 pathway and impairment of immune responses with the CSFV infection, the mRNA expression of PD-1 and its ligands were evaluated by quantitative polymerase chain reaction (qPCR) during artificial CSFV infection. Simultaneously, expression of IL-2 and IL-10 mRNA were detected. The T cell proliferation and CSFV load in plasma were also measured. Results showed that the expression of PD-1 and its ligands mRNA were significantly increased (p?

To further understand the effect of co-infection of subgroup J avian leukosis virus (ALV-J) and reticuloendotheliosis virus (REV) in specific-pathogen-free (SPF) white leghorn chickens, the experiment was made to study the pathogenicity, the weight of body and immune organs, response to newcastle disease virus (NDV) and avian influenza virus subtype H9 (AIV-H9) vaccination. Chickens were randomly divided into four groups, which includes injection groups (REV, ALV-J, REV plus ALV-J), and negative control group. The pathogenesis experiments indicated that chickens co-infected with REV and ALV-J had significantly higher mortality rate than those of the chickens infected with REV or ALV-J alone (P < 0.05). Chickens inoculated with REV and ALV-J had significantly lower weights than chickens in all other groups (P < 0.05). There were no significant differences between the two single infection groups and co-infection group (P > 0.05) on bursa and thymus over body wt ratios, however, chickens co-infected with REV and ALV-J had significantly lower titers than REV-infected chickens and ALV-J-infected chickens on HI antibody titers to ND and AIV-H9 after vaccination (P < 0.05). These findings suggested that the co-infection of REV and ALV-J caused more serious growth retardation and immunosuppression in SPF chickens. [ABSTRACT FROM AUTHOR]

The very largeGprotein-coupled receptor 1 (VLGR1) is a core component in inner ear hair cell development. Mutations in the vlgr1 gene cause Usher syndrome, the symptoms of which include congenital hearing loss and progressive retinitis pigmentosa. However, the mechanism of VLGR1-regulated intracellular signaling and its role in Usher syndrome remain elusive. Here, we show that VLGR1 is processed into two fragments after autocleavage at the G protein-coupled receptor proteolytic site. The cleaved VLGR1 β-subunit constitutively inhibited adenylate cyclase (AC) activity through Gαi coupling. Co-expression of the Gαiq chimera with the VLGR1 β-subunit changed its activity to the phospholipase C/nuclear factor of activated T cells signaling pathway, which demonstrates the Gαi protein coupling specificity of this subunit. An R6002A mutation in intracellular loop 2 of VLGR1 abolished Gαi coupling, but the pathogenic VLGR1 Y6236fsx1 mutant showed increased AC inhibition. Furthermore, overexpression of another Usher syndrome protein, PDZD7, decreased the AC inhibition of the VLGR1 β-subunit but showed no effect on the VLGR1 Y6236fsx1 mutant. Taken together, we identified an independentG αi signaling pathway of the VLGR1β-subunit and its regulatory mechanisms that may have a role in the development of Usher syndrome. [ABSTRACT FROM AUTHOR]

Background aims. Defocused low-energy shock wave (DLSW) therapy has shown effectiveness in regenerative medicine. The mechanism of action was mainly focused on the pathophysiological improvement at the wound tissues. In this study, the activation of stem cells treated by DLSW was first examined as an important pathway during the healing process. Methods. Cultured rat bone marrow-derived mesenchymal stromal cells (BMSC) were treated by DLSW before each passage. The untreated BMSC served as a control. The secretions of vascular endothelial growth factor (VEGF) and CXC ligand 5 (CXCL5) were tested by means of enzyme-linked immunoassay. Flow cytometry was performed to analyze the BMSC (passage 4) surface antigen expressions (CD 166, CD44 and CD34). The expressions of proliferating cell nuclear antigen and Ki67 were analyzed by means of Western blot. The healing abilities of conditioned media of shocked and unshocked BMSC were examined by Matrigel-based capillary-like tube formation assay and rat major pelvic ganglia culture test. Results. The shocked BMSC secreted more VEGF and CXCL5 than did those of unshocked BMSC. The expressions of CD 166, CD44 and CD34 showed no significant differences (P > 0.05) between the shocked and unshocked BMSC. The shocked BMSC demonstrated higher expressions of proliferating cell nuclear antigen (P < 0.01) and Ki67 (P < 0.01) than did those of unshocked BMSC. The shocked BMSC conditioned medium showed higher ability to enhance the growth of major pelvic ganglia neurites (P < 0.05) and Matrigel-based endothelial tube-like formation (P < 0.05). Conclusions. DLSW did not interfere with the expressions of cell surface markers. DLSW enhanced the secretion and proliferation of BMSC and promoted angiogenesis and nerve regeneration in vitro. [ABSTRACT FROM AUTHOR]

A missense single-nucleotide polymorphism in the gene encoding the lymphoid-specific tyrosine phosphatase (Lyp) has been identified as a causal factor in a wide spectrum of autoim- mune diseases. Interestingly, the autoimmune-predisposing variant of Lyp appears to represent a gain-of-function mutation, implicating Lyp as an attractive target for the development of effective strategies for the treatment of many autoimmune dis- orders. Unfortunately, the precise biological functions of Lyp in signaling cascades and cellular physiology are poorly under- stood. Identification and characterization of Lyp substrates will help define the chain of molecular events coupling Lyp dys- function to diseases. In the current study, we identified consen- sus sequence motifs for Lyp substrate recognition using an "inverse alanine scanning" combinatorial library approach. The intrinsic sequence specificity data led to the discovery and characterization of SKAP-HOM, a cytosolic adaptor protein required for proper activation of the immune system, as a bona fide Lyp substrate. To determine the molecular basis for Lyp substrate recognition, we solved crystal structures of Lyp in complex with the consensus peptide as well as the phosphopep- tide derived from SKAP-HOM. Together with the biochemical data, the structures define the molecular determinants for Lyp substrate specificity and provide a solid foundation upon which novel therapeutics targeting Lyp can be developed for multiple autoimmune diseases. [ABSTRACT FROM AUTHOR]

Phosphatase of regenerating liver 3 (PRL3) is overexpressed in a variety of tumors, and high levels of PRL3 expression are associated with tumorigenesis and metastasis. Consistent with an oncogenic role for PRL3, we show that ectopic PRL3 expression promotes cell proliferation and invasion. However, little is known about the molecular basis for PRL3 function. Obtaining this knowledge is vital for understanding PRL3-mediated disease processes and for the development of novel anticancer therapies targeted to PRL3. Here we report that up-regulation of PRL3 activates the Src kinase, which initiates a number of signal pathways culminating in the phosphorylation of ERK1/2, STAT3, and p130Cas. The activation of these pathways likely contributes to the increased cell growth and motility of PRL3 cells. We provide evidence that PRL3 induces Src activation through down-regulation of Csk, a negative regulator of Src. Importantly, Src activation and Csk down-regulation are also observed in colon cancer cells expressing a higher level of PRL3. Thus, we have revealed a biochemical mechanism for the PRL3-mediated cell invasion and proliferation in which elevated PRL3 expression causes a reduction in Csk level, leading to Src activation. [ABSTRACT FROM AUTHOR]