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Flavonoids are well known as a large class of polyphenolic compounds, which have a variety of physiological activities, including anti-influenza virus activity. The influenza A/WSN/33 infected A549 cells have been used to screen anti-influenza virus drugs from natural flavonoid compounds library. Unexpectedly, some flavonoid compounds significantly inhibited virus replication, while the others dramatically promoted virus replication. In this study, we attempted to understand these differences between flavonoid compounds in their antivirus mechanisms. Hesperidin and kaempferol were chosen as representatives of both sides, each of which exhibited the opposite effects on influenza virus replication. Our investigation revealed that the opposite effects produced by hesperidin and kaempferol on influenza virus were due to inducing the opposite cell-autonomous immune responses by selectively modulating MAP kinase pathways: hesperidin up-regulated P38 and JNK expression and activation, thus resulting in the enhanced cell-autonomous immunity; while kaempferol dramatically down-regulated p38 and JNK expression and activation, thereby suppressing cell-autonomous immunity. In addition, hesperidin restricted RNPs export from nucleus by down-regulating ERK activation, but kaempferol promoted RNPs export by up-regulating ERK activation. Our findings demonstrate that a new generation of anti-influenza virus drugs could be developed based on selective modulation of MAP kinase pathways to stimulate cell-autonomous immunity. [ABSTRACT FROM AUTHOR]

Taking English teaching summative assessment and formative assessment system as the entry point, the essay illustrates the effect of the assessments on College English teaching and its great influence on English learning by combing it with practical teaching experience deeply and broadly. It also points out that students' real English level can not only rely on a single evaluation mode. Summative assessment and formative assessment have different form and different function. They should be combined together during the teaching and learning process. Then the students' English level will be effectively evaluated, and it will better guide the foreign language teaching. [ABSTRACT FROM AUTHOR]

In Pseudomonas aeruginosa PAO1, the pvdQ gene has been shown to have at least two functions. It encodes the acylase enzyme and hydrolyzes 3-oxo-C12-HSL, the key signaling molecule of quorum sensing system. In addition, pvdQ is involved in swarming motility. It is required for up-regulated during swarming motility, which is triggered by high cell densities. As high-density bacterial populations also display elevated antibiotic resistance, studies have demonstrated that swarm-cell differentiation in P. aeruginosa promotes increased resistance to various antibiotics. PvdQ acts as a signal during swarm-cell differentiation, and thus may play a role in P. aeruginosa antibiotic resistance. The aim of this study is to examine whether pvdQ was involved in modifying antibiotic susceptibility during swarming conditions, and to investigate the mechanism by which this occurred. We constructed the PAO1pME pvdQ strain, which overproduced PvdQ. PAO1pME pvdQ promotes swarming motility, while PAO1Δ pvdQ abolishes swarming motility. In addition, both PAO1 and PAO1pME pvdQ acquired resistance to ceftazidime, ciprofloxacin, meropenem, polymyxin B, and gentamicin, though PAO1pME pvdQ exhibited a two to eightfold increase in antibiotic resistance compared to PAO1. These results indicate that pvdQ plays an important role in elevating antibiotic resistance via swarm-cell differentiation and possibly other mechanisms as well. We analyzed outer membrane permeability. Our data also suggest that pvdQ decreases P. aeruginosa outer membrane permeability, thereby elevating antibiotic resistance under swarming conditions. Our results suggest new approaches for reducing P. aeruginosa resistance. [ABSTRACT FROM AUTHOR]

The article presents a study regarding the correlation of antithrombin gene Arg197Stop mutation and venous sinus thrombosis in a Chinese family. The study is investigated a nonsense mutation from C to T on locus 6431 in exon 3B of the antithrombin gene. The study has found that the ineffective heparin therapy in the propositus patient is correlated with a lack heparin binding sites following an antithrombin gene mutation.

Hongloumeng by Xueqin Cao (Hsueh-ch‘in Ts'ao) is generally considered one of the greatest classical Chinese novel. Of all nine published English translations known today, the one translated by Hawkes and Minford (the Story of the Stone, Penguin, 1973–86) and the other by Yang and Yang (A Dream of Red Mansions1, Foreign Languages Press in Beijing, 1978–80) are the best known among translators and literary scholars. Over the years, both have been carefully scrutinized and much critiqued. Translators and translation scholars have been engaged in heated debates over salient features of the translations, strategies employed by the translators, the possible effects of the two translations and so on [cf. Liu and Gu (1997) On translation of cultural contents in Hong Lou Meng [in Chinese]. Chinese Translators Journal, 1: 16–19; Wang (2001) A Comparative Study of the English Translations of Poetry in Hong Lou Meng. Xi’an: Shanxi Normal University Press; Feng (2006) On the Translation of Hong Lou Meng [in Chinese]. Shanghai: Shanghai Foreign Language Education Press; Liu (2008), Translating tenor: With reference to the English versions of Hong Lou Meng. Meta, 53(3): 528–48], with the eventual aim to determine which translation better captures the style of the original text or author. Like many debates of similar nature, no definitive conclusions have been reached despite such an intense interest. We believe a corpus-assisted examination [Baker, M. (2000). Towards a methodology for investigating the style of a literary translator. Target, 12(2): 241–66; Baker, M. (1993). Corpus linguistics and translation studies: Implications and applications. In Gill, F., Baker, M., and Tognini-Bonelli, E. (eds), Text and Technology: In Honour of John Sinclair. Amsterdam: Benjamins, pp. 233–50] of the two translations will provide more convincing analysis and can better describe the differences in the translation style of the two famous translations. A particular effort is further made to interpret the reasons for the different strategies adopted by the two different pairs of translators in the social, political, and ideological context of the translations. [ABSTRACT FROM AUTHOR]

In Arabidopsis thaliana ( Arabidopsis) treated with the harpin protein HrpN, resistance to the green peach aphid Myzus persicae, a generalist phloem-feeding insect, develops with induced expression of the AtMYB44 gene. Special GLUCAN SYNTHESIS-LIKE ( GSL) genes and β-1,3-glucan callose play an important role in plant defence responses to attacks by phloem-feeding insects. Here we report that AtGLS5 and AtMYB44 are both required for HrpN-induced repression of M. persicae feeding from the phloem of Arabidopsis leaves. In 24 h successive surveys on large-scale aphid populations, the proportion of feeding aphids was much smaller in HrpN-treated plants than in control plants, and aphids preferred to feed from the 37 tested atgsl mutants rather than the wild-type plant. The atgsl mutants were generated previously by mutagenesis in 12 identified AtGSL genes ( AtGSL1 through AtGSL12); in the 24 h survey, both atgsl5 and atgsl6 tolerated aphid feeding, and atgsl5 was the most tolerant. Consistently, atgsl5 was also most inhibitive to the deterrent effect of HrpN on the phloem-feeding activity of aphids as monitored by the electrical penetration graph technique. These results suggested an important role of the AtGSL5 gene in the effect of HrpN. In response to HrpN, AtGSL5 expression and callose deposition were induced in the wild-type plant but not in atgsl5. In response to HrpN, moreover, the AtMYB44 gene known to be required for repression of aphid reproduction on the plant was also required for repression of the phloem-feeding activity. Small amounts of the AtGSL5 transcript and callose deposition were detected in the atmyb44 mutant, as in atgsl5. Both mutants performed similarly in tolerating the phloem-feeding activity and impairing the deterrent effect of HrpN, suggesting that AtGSL5 and AtMYB44 both contributed to the effect. [ABSTRACT FROM AUTHOR]

Background: Treatment of plants with HrpNEa, a protein of harpin group produced by Gram-negative plant pathogenic bacteria, induces plant resistance to insect herbivores, including the green peach aphid Myzus persicae, a generalist phloem-feeding insect. Under attacks by phloem-feeding insects, plants defend themselves using the phloem-based defense mechanism, which is supposed to involve the phloem protein 2 (PP2), one of the most abundant proteins in the phloem sap. The purpose of this study was to obtain genetic evidence for the function of the Arabidopsis thaliana (Arabidopsis) PP2-encoding gene AtPP2-A1 in resistance to M. persicae when the plant was treated with HrpNEa and after the plant was transformed with AtPP2-A1. Results: The electrical penetration graph technique was used to visualize the phloem-feeding activities of apterous agamic M. persicae females on leaves of Arabidopsis plants treated with HrpNEa and an inactive protein control, respectively. A repression of phloem feeding was induced by HrpNEa in wild-type (WT) Arabidopsis but not in atpp2-a1/E/142, the plant mutant that had a defect in the AtPP2-A1 gene, the most HrpNEa-responsive of 30 AtPP2 genes. In WT rather than atpp2-a1/E/142, the deterrent effect of HrpNEa treatment on the phloem-feeding activity accompanied an enhancement of AtPP2-A1 expression. In PP2OETAt (AtPP2-A1-overexpression transgenic Arabidopsis thaliana) plants, abundant amounts of the AtPP2-A1 gene transcript were detected in different organs, including leaves, stems, calyces, and petals. All these organs had a deterrent effect on the phloem-feeding activity compared with the same organs of the transgenic control plant. When a large-scale aphid population was monitored for 24 hours, there was a significant decrease in the number of aphids that colonized leaves of HrpNEatreated WT and PP2OETAt plants, respectively, compared with control plants. Conclusions: The repression in phloem-feeding activities of M. persicae as a result of AtPP2-A1 overexpression, and as a deterrent effect of HrpNEa treatment in WT Arabidopsis rather than the atpp2-a1/E/142 mutant suggest that AtPP2-A1 plays a role in plant resistance to the insect, particularly at the phloem-feeding stage. The accompanied change of aphid population in leaf colonies suggests that the function of AtPP2-A1 is related to colonization of the plant. [ABSTRACT FROM AUTHOR]

The harpin protein HrpN induces Arabidopsis resistance to the green peach aphid by activating the ethylene signalling pathway and by recruiting EIN2, an essential regulator of ethylene signalling, for a defence response in the plant. We investigated 37 ethylene-inducible Arabidopsis transcription factor genes for their effects on the activation of ethylene signalling and insect defence. Twenty-eight of the 37 genes responded to both ethylene and HrpN, and showed either increased or inhibited transcription, while 18 genes showed increased transcription not only by ethylene but also by HrpN. In response to HrpN, transcription levels of 22 genes increased, with AtMYB44 being the most inducible, six genes had decreased transcript levels, and nine remained unchanged. When Arabidopsis mutants previously generated by mutagenicity at the 37 genes were surveyed, 24 mutants were similar to the wild type plant while four mutants were more resistant and nine mutants were more susceptible than wild type to aphid infestation. Aphid-susceptible mutants showed a greater susceptibility for atmyb15, atmyb38 and atmyb44, which were generated previously by T-DNA insertion into the exon region of AtMYB15 and the promoter regions of AtMYB38 and AtMYB44. The atmyb44 mutant was the most susceptible to aphid infestation and most compromised in induced resistance. Resistance accompanied the expression of PDF1.2, an ethylene signalling marker gene that requires EIN2 for transcription in wild type but not in atmyb15, atmyb38, and atmyb44, suggesting a disruption of ethylene signalling in the mutants. However, only atmyb44 incurred an abrogation in induced EIN2 expression, suggesting a close relationship between AtMYB44 and EIN2. [ABSTRACT FROM AUTHOR]

To investigate the self-assembly of polyethylene glycol (PEG)-phosphatidylethanolamine (PE) conjugate with water-soluble drugs (doxorubicin hydrochloride, vinorelbine tartrate and vincristine sulfate) and give insight into the mechanism of formation and mode of interaction of the drug with PEG-PE as well as the general principles of self-assembly using pegylated lipid micelles. One-step self-assembly method to prepare drug-loaded micelles was developed. The micelles were characterized by dynamic light scattering, transmission electron microscopy, encapsulation efficiency, and release study. NMR was used to study molecular assembly of PEG-PE with doxorubicin. Doxorubicin hydrochloride and vinorelbine tartrate were entrapped into micelles with high efficiency of >99.0% at molar ratios of 1:1 and 2:1 of PEG-PE to drugs, respectively. Drug loading did not measurably perturb either the geometry or the size. It was found that electrostatic interaction and hydrophobic forces are responsible for the intercalation of drugs into PEG-PE micelles. NMR data revealed that the anthracycline ring of doxorubicin was inserted between PE phospholipids, and its amino sugar located in the outer shell of micelle between PEG chains. Based on our results, the structure and self-assembly mechanism of water-soluble drugs encapsulated in PEG-PE micelles were proposed. [ABSTRACT FROM AUTHOR]

A weathering steel Cu–P–Cr–Ni–Mo has been developed which exhibits special continuous cooling transformation characteristics which permit the desired dual-phase (DP) microstructure to be obtained by direct hot-rolling. Hot-rolling procedures to obtain DP microstructures have been designed based on the continuous cooling transformation diagram of weathering steel Cu–P–Cr–Ni–Mo. The results show that the microstructures of DP weathering steels Cu–P–Cr–Ni–Mo are characterized by an irregular distribution of island-shaped martensite–austenite in the matrix of polygonal ferrite grains. DP weathering steel Cu–P–Cr–Ni–Mo with favorable corrosion resistant property, weldability and mechanical properties, such as, high strain hardening exponent values, a lower ratio of yield to tensile strength, and higher strengths; and is obtained successfully by direct hot-rolling. [ABSTRACT FROM AUTHOR]

Porcine circovirus type 2 (PCV2) and the associated disease postweaning multisystemic wasting syndrome (PMWS) have caused heavy losses in global agriculture in recent decades. Rapid detection of PCV2 is very important for the effective prophylaxis and treatment of PMWS. To establish a sensitive, specific assay for the detection and quantitation of PCV2, we designed and synthesized specific primers and a probe in the open reading frame 2. The assay had a wide dynamic range with excellent linearity and reliable reproducibility, and detected between 10² and 1010 copies of the genomic DNA per reaction. The coefficient of variation for Ct values varied from 0.59% to 1.05% in the same assay and from 1.9% to 4.2% in 10 different assays. The assay did not cross-react with porcine circovirus type 1, porcine reproductive and respiratory, porcine epidemic diarrhea, transmissible gastroenteritis of pigs and rotavirus. The limits of detection and quantitation were 10 and 100 copies, respectively. Using the established real-time PCR system, 39 of the 40 samples we tested were detected as positive. [ABSTRACT FROM AUTHOR]

Primary mediastinal seminoma often occurs in the anterior mediastinum of young males. It is unusual for the tumor to originate in the middle or posterior mediastinum, and such cases have rarely been reported in the English literature. The present study reports the case of a 52-year-old man with a 3.0-cm primary seminoma arising in the middle mediastinum. The patient presented with the symptoms of cough and chest tightness. Fluorine-18 fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) scans revealed unique abnormal FDG uptake in the middle mediastinum. A mediastinoscopy was performed and integral excision was found to be difficult. A biopsy was performed and the histological examination revealed a primary seminoma. Following 4 cycles of a standard bleomycin, etoposide and cisplatin chemotherapy regimen, and chest irradiation at a total dose of 40 Gy in 20 fractions, the tumor exhibited a partial response, decreasing in size, and FDG uptake was no longer observed on 18F-FDG-PET scan. The last follow-up date was April 2016 and the patient has remained disease-free for 20 months. [ABSTRACT FROM AUTHOR]

HrpNEa is a harpin protein from Erwinia amylovora, a bacterial pathogen that causes fire blight in rosaceous plants. Treating plants with HrpNEa stimulates ethylene and abscisic acid (ABA) to induce plant growth and drought tolerance, respectively. Herein, we report that both growth hormones cooperate to mediate the role of HrpNEa in promoting root growth of Arabidopsis thaliana seedlings. Root growth is promoted coordinately with elevation in levels of ABA and ethylene subsequent to soaking of germinating seeds of wild-type (WT) Arabidopsis in a solution of HrpNEa. However, these responses are arrested by inhibiting WT roots from synthesizing ethylene as well as sensing of ABA and ethylene. The effects of HrpNEa on roots are also nullified in ethylene-insensitive etr1- 1 and ein5- 1 mutants and in the ABA-insensitive mutant abi2- 1 of Arabidopsis. These results provide evidence for presence of a relationship between root growth enhancement and signaling by ABA and ethylene in response to HrpNEa. Nevertheless, when HrpNEa is applied to leaves, ethylene signaling is active in the absence of ABA signaling to promote plant growth. This suggests the presence of a different signaling mechanism in leaves from that in roots. [ABSTRACT FROM AUTHOR]

In the adult rodent, stroke induces an increase in endogenous neural progenitor cell (NPC) proliferation in the subventricular zone (SVZ) and neuroblasts migrate towards the ischemic boundary. We investigated the role of stromal cell-derived factor 1α (SDF-1α) in mediating NPC migration after stroke. We found that cultured NPCs harvested from the normal adult SVZ, when they were overlaid onto stroke brain slices, exhibited significantly (P<0.01) increased migration (67.2±25.2 μm) compared with the migration on normal brain slices (29.5±29.5 μm). Immunohistochemistry showed that CXCR 4, a receptor of SDF-1α, is expressed in the NPCs and migrating neuroblasts in stroke brain. Blocking SDF-1α by a neutralizing antibody against CXCR 4 significantly attenuated stroke-enhanced NPC migration. ELISA analysis revealed that SDF-1α levels significantly increased (P<0.01) in the stroke hemisphere (43.6±6.5 pg/mg) when compared with the normal brain (25.2±1.9 pg/mg). Blind-well chamber assays showed that SDF-1α enhanced NPC migration in a dose-dependent manner with maximum migration at a dose of 500 ng/mL. In addition, SDF-1α induced directionally selective migration. These findings show that SDF-1α generated in the stroke hemisphere may guide NPC migration towards the ischemic boundary via binding to its receptor CXCR 4 in the NPC. Thus, our data indicate that SDF-1α/CXCR 4 is important for mediating specific migration of NPCs to the site of ischemic damaged neurons.Journal of Cerebral Blood Flow & Metabolism (2006) 26, 125–134. doi:10.1038/sj.jcbfm.9600172; published online 15 June 2005 [ABSTRACT FROM AUTHOR]

Here, we investigate the effects of endothelial nitric oxide synthase (eNOS) on angiogenesis, neurogenesis, neurotrophic factor expression, and neurological functional outcome after stroke. Wild-type and eNOS knock-out (eNOS-/-) mice were subjected to permanent occlusion of the right middle cerebral artery, eNOS-/- mice exhibited more severe neurological functional deficit after stroke than wild-type mice. Decreased subventricular zone (SVZ) progenitor cell proliferation and migration, measured using bromodeoxyuridine, Ki-67, nestin, and doublecortin immunostaining in the ischemic brain, and decreased angiogenesis, as demonstrated by reduced endothelial cell proliferation, vessel perimeter, and vascular density in the ischemic border, were evident in eNOS-/- mice compared with wild-type mice. eNOS-deficient mice also exhibited a reduced response to vascular endothelial growth factor (VEGF)-induced angiogenesis in a corneal assay. ELISAs showed that eNOS-/- mice have decreased brain-derived neurotrophic factor (BDNF) expression but not VEGF and basic fibroblast growth factor in the ischemic brain compared with wild-type mice. In addition, cultured SVZ neurosphere formation, proliferation, telomerase activity, and neurite outgrowth but not cell viability from eNOS-/- mice were significantly reduced compared with wild-type mice. BDNF treatment of SVZ cells derived from eNOS-/- mice restored the decreased neurosphere formation, proliferation, neurite outgrowth, and telomerase activity in cultured eNOS- /- SVZ neurospheres. SVZ explant cell migration also was significantly decreased in eNOS-/- mice compared with wild-type mice. These data indicate that eNOS is not only a downstream mediator for VEGF and angiogenesis but also regulates BDNF expression in the ischemic brain and influences progenitor cell proliferation, neuronal migration, and neurite outgrowth and affects... [ABSTRACT FROM AUTHOR]

Molecular mechanisms underlying the role of statins in the induction of brain plasticity and subsequent improvement of neurologic outcome after treatment of stroke have not been adequately investigated. Here, we use both in vivo and in vitro studies to investigate the potential roles of two prominent factors, vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF), in mediating brain plasticity after treatment of stroke with atorvastatin. Treatment of stroke in adult mice with atorvastatin daily for 14 days, starting at 24 hours after MCAO, shows significant improvement in functional recovery compared with control animals. Atorvastatin increases VEGF, VEGFR2 and BDNF expression in the ischemic border. Numbers of migrating neurons, developmental neurons and synaptophysin-positive cells as well as indices of angiogenesis were significantly increased in the atorvastatin treatment group, compared with controls. In addition, atorvastatin significantly increased brain subventricular zone (SVZ) explant cell migration in vitro. Anti-BDNF antibody significantly inhibited atorvastatin-induced SVZ explant cell migration, indicating a prominent role for BDNF in progenitor cell migration. Mouse brain endothelial cell culture expression of BDNF and VEGFR2 was significantly increased in atorvastatin-treated cells compared with control cells. Inhibition of VEGFR2 significantly decreased expression of BDNF in brain endothelial cells. These data indicate that atorvastatin promotes angiogenesis, brain plasticity and enhances functional recovery after stroke. In addition, VEGF, VEGFR2 and BDNF likely contribute to these restorative processes.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 281–290. doi:10.1038/sj.jcbfm.9600034 [ABSTRACT FROM AUTHOR]

The orientation of mitotic cleavage regulates neurogenesis during neural development. We examined the orientation of mitotic cleavage of dividing progenitor cells in the subventricular zone (SVZ) of adult rats subjected to stroke. In nonstroke rats, 55% of dividing cells were oriented horizontally, whereas 40% were oriented vertically. Horizontal and vertical cleavage orientations produce asymmetric and symmetric divisions, respectively. Four days after stroke, the number of dividing cells increased twofold, whereas the proportion of symmetric dividing cells significantly (p < 0.01) increased from 40% before stroke to 60%. Fourteen days after stroke, the percentage of symmetric dividing cells was 47%. Stroke-increased numbers of dividing cells in M-phase were confirmed by immuostaining. In nonstroke rats, 37 and 33% of symmetric and asymmetric dividing cells, respectively, exhibited a neuronal marker (TuJ1). Four days after stroke, rats exhibited a significant (p < 0.05) augmentation of the frequency (47%) of neuronal distribution showing TuJ1 immunoreactivity in ceils with symmetric division but not ceils with asymmetric division (33%). Numb immunoreactivity was detected in SVZ cells of nonstroke rats. Stroke did not change Numb distribution. Our data suggest that neurons are produced by both asymmetric and symmetric cell divisions in the adult SVZ, and the transient increases in symmetric division and neuronal differentiation may result in stroke-induced neurogenesis. [ABSTRACT FROM AUTHOR]

The subtilisin-like prohormone convertases (PCs) contain an essential downstream domain (P domain), which has been predicted to have a β-barrel structure that interacts with and stabilizes the catalytic domain (CAT). To assess possible sites of hydrophobic interaction, a series of mutant PC3-enhanced GFP constructs were prepared in which selected nonpolar residues on the surface of CAT were substituted by the corresponding polar residues in subtilisin Carlsberg. To investigate the folding potential of the isolated P domain, signal peptide—P domain-enhanced GFP constructs with mutated and/or truncated P domains were also made. All mutants were expressed in βTC3 cells, and their subcellular localization and secretion were determined. The mutants fell into three main groups: (i) Golgi/ secreted, (ii) ER/nonsecreted, and (iii) apoptosis inducing. The destabilizing CAT mutations indicate that the side chains of V292, T328, L351, Q408, H409, V412, and F441 and nonpolar fragments of the side chains of R405 and W413 form a hydrophobic patch on CAT that interacts with the P domain. We also have found that the P domain can fold independently, as indicated by its secretion. Interestingly, T594, which is near the P domain C terminus, was not essential for P domain secretion but is crucial for the stability of intact PC3. T594V produced a stable enzyme, but T594D did not, which suggests that T594 participates in important hydrophobic interactions within PC3. These findings support our conclusion that the catalytic and P domains contribute to the folding and thermodynamic stability of the convertases through reciprocal hydrophobic interactions. [ABSTRACT FROM AUTHOR]

Examines the influence of protein convertases (PC) on the development of dwarfism and multiple neuroendocrine peptide processing defects among mice. Role of PC1 and PC2 in peptide hormone processing; Involvement of PC1/3 in the biosynthesis of neuropeptides; Performance of pituitary metabolic labeling experiments.

Type 2 diabetes (T2D) is potentially linked to disordered tryptophan metabolism that attributes to the intricate interplay among diet, gut microbiota, and host physiology. However, underlying mechanisms are substantially unknown. Comparing the gut microbiome and metabolome differences in mice fed a normal diet (ND) and high-fat diet (HFD), we uncover that the gut microbiota-dependent tryptophan metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) is present at lower concentrations in mice with versus without insulin resistance. We further demonstrate that the microbial transformation of tryptophan into 5-HIAA is mediated by Burkholderia spp. Additionally, we show that the administration of 5-HIAA improves glucose intolerance and obesity in HFD-fed mice, while preserving hepatic insulin sensitivity. Mechanistically, 5-HIAA promotes hepatic insulin signaling by directly activating AhR, which stimulates TSC2 transcription and thus inhibits mTORC1 signaling. Moreover, T2D patients exhibit decreased fecal levels of 5-HIAA. Our findings identify a noncanonical pathway of microbially producing 5-HIAA from tryptophan and indicate that 5-HIAA might alleviate the pathogenesis of T2D. [ABSTRACT FROM AUTHOR]

Sample-wise deconvolution methods estimate cell-type proportions and gene expressions in bulk tissue samples, yet their performance and biological applications remain unexplored, particularly in human brain transcriptomic data. Here, nine deconvolution methods were evaluated with sample-matched data from bulk tissue RNA sequencing (RNA-seq), single-cell/nuclei (sc/sn) RNA-seq, and immunohistochemistry. A total of 1,130,767 nuclei per cells from 149 adult postmortem brains and 72 organoid samples were used. The results showed the best performance of dtangle for estimating cell proportions and bMIND for estimating sample-wise cell-type gene expressions. For eight brain cell types, 25,273 cell-type eQTLs were identified with deconvoluted expressions (decon-eQTLs). The results showed that decon-eQTLs explained more schizophrenia GWAS heritability than bulk tissue or single-cell eQTLs did alone. Differential gene expressions associated with Alzheimer's disease, schizophrenia, and brain development were also examined using the deconvoluted data. Our findings, which were replicated in bulk tissue and single-cell data, provided insights into the biological applications of deconvoluted data in multiple brain disorders. [ABSTRACT FROM AUTHOR]

Background: Targeting the TGF-β1 pathway for breast cancer metastasis therapy has become an attractive strategy. We have previously demonstrated that naringenin significantly reduced TGF-β1 levels in bleomycin-induced lung fibrosis and effectively prevented pulmonary metastases of tumors. This raised the question of whether naringenin can block TGF-β1 secretion from breast cancer cells and inhibit their pulmonary metastasis.Methods: We transduced a lentiviral vector encoding the mouse Tgf-β1 gene into mouse breast carcinoma (4T1-Luc2) cells and inoculated the transformant cells (4T1/TGF-β1) into the fourth primary fat pat of Balb/c mice. Pulmonary metastases derived from the primary tumors were monitored using bioluminescent imaging. Spleens, lungs and serum (n = 18-20 per treatment group) were analyzed for immune cell activity and TGF-β1 level. The mechanism whereby naringenin decreases TGF-β1 secretion from breast cancer cells was investigated at different levels, including Tgf-β1 transcription, mRNA stability, translation, and extracellular release.Results: In contrast to the null-vector control (4T1/RFP) tumors, extensive pulmonary metastases derived from 4T1/TGF-β1 tumors were observed. Administration of the TGF-β1 blocking antibody 1D11 or naringenin showed an inhibition of pulmonary metastasis for both 4T1/TGF-β1 tumors and 4T1/RFP tumors, resulting in increased survival of the mice. Compared with 4T1/RFP bearing mice, systemic immunosuppression in 4T1/TGF-β1 bearing mice was observed, represented by a higher proportion of regulatory T cells and myeloid-derived suppressor cells and a lower proportion of activated T cells and INFγ expression in CD8(+) T cells. These metrics were improved by administration of 1D11 or naringenin. However, compared with 1D11, which neutralized secreted TGF-β1 but did not affect intracellular TGF-β1 levels, naringenin reduced the secretion of TGF-β1 from the cells, leading to an accumulation of intracellular TGF-β1. Further experiments revealed that naringenin had no effect on Tgf-β1 transcription, mRNA decay or protein translation, but prevented TGF-β1 transport from the trans-Golgi network by inhibiting PKC activity.Conclusions: Naringenin blocks TGF-β1 trafficking from the trans-Golgi network by suppressing PKC activity, resulting in a reduction of TGF-β1 secretion from breast cancer cells. This finding suggests that naringenin may be an attractive therapeutic candidate for TGF-β1 related diseases. [ABSTRACT FROM AUTHOR]

Leaf trichomes serve as a physical barrier and can also secrete antimicrobial compounds to protect plants from attacks by insects and pathogens. Besides the use of the physical and chemical mechanisms, leaf trichomes might also support plant responses by communicating the extrinsic cues to plant intrinsic signalling pathways. Here we report a role of leaf trichomes in tobacco (Nicotiana tabacum) hypersensitive cell death (HCD) induced by ParA1, an elicitin protein from a plant-pathogenic oomycete. After localized treatment with ParA1, reactive oxygen species were produced first in the leaf trichomes and then in mesophylls. Reactive oxygen species are a group of intracellular signals that are crucial for HCD to develop and for cells to undergo cell death subsequent to chromatin condensation, a hallmark of HCD. These events were impaired when the production of hydrogen peroxide (H2O2) was inhibited by catalase or a NADPH-oxidase inhibitor applied to trichomes, suggesting the importance of H2O2 in the pathway of HCD signal transduction from the trichomes to mesophylls. This pathway was no longer activated when leaf trichomes were treated with C51S, a ParA1 mutant protein defective in its interaction with N. tabacum TTG1 (NtTTG1), which is a trichome protein that binds ParA1, rather than C51S, in vitro and in trichome cells. The ParA1-NtTTG1 interaction and the HCD pathway were also abrogated when NtTTG1 was silenced in the trichomes. These observations suggest that NtTTG1 plays an essential role in HCD signal transduction from leaf trichomes to mesophylls [ABSTRACT FROM AUTHOR]

Plants employ aquaporins (AQPs) of the plasma membrane intrinsic protein (PIP) family to import environmental substrates, thereby affecting various processes, such as the cellular responses regulated by the signaling molecule hydrogen peroxide (H2O2). Common wheat (Triticum aestivum) contains 24 candidate members of the PIP family, designated as TaPIP1;1 to TaPIP1;12 and TaPIP2;1 to TaPIP2;12. None of these TaPIP candidates have been characterized for substrate selectivity or defense responses in their source plant. Here, we report that T. aestivum AQP TaPIP2;10 facilitates the cellular uptake of H2O2 to confer resistance against powdery mildew and Fusarium head blight, two devastating fungal diseases in wheat throughout the world. In wheat, the apoplastic H2O2 signal is induced by fungal attack, while TaPIP2;10 is stimulated to translocate this H2O2 into the cytoplasm, where it activates defense responses to restrict further attack. TaPIP2;10-mediated transport of H2O2 is essential for pathogen-associated molecular pattern-triggered plant immunity (PTI). Typical PTI responses are induced by the fungal infection and intensified by overexpression of the TaPIP2;10 gene. TaPIP2;10 overexpression causes a 70% enhancement in wheat resistance to powdery mildew and an 86% enhancement in resistance to Fusarium head blight. By reducing the disease severities, TaPIP2;10 overexpression brings about >37% increase in wheat grain yield. These results verify the feasibility of using an immunity-relevant AQP to concomitantly improve crop productivity and immunity. [ABSTRACT FROM AUTHOR]

In order to solve the problem of interaction between multiple evaluation indexes of seed metering performance under multiple factors of centralized seed feeding device, a multi-objective optimization of structure based on particle swarm optimization (PSO) algorithm was proposed in this paper. The wheat centralized seed feeding device was taken as the research object, and the experimental factors were cone angle of type hole, working speed and seed filling gap. The working process of wheat centralized seed feeding device was simulated by discrete element method (DEM). The average seed number of type hole, the variation coefficient of the average seed number of type hole, and the maximum tangential force between seed and seed feeding mechanism were selected as the evaluation indexes. Through the variance analysis of the evaluation indexes by the experimental factors, the optimization objective function was constructed. Using PSO algorithm, the multi-objective optimization was carried out for the wheat centralized seed feeding device. The optimization results show that the best structural combination parameters of the wheat centralized seed feeding device are the hole cone angle of 31.6° and the seed filling gap of 4.6 mm. The validity of the method was verified by simulation and field test. The results show that the PSO algorithm multi-objective optimization method proposed in this paper can provide a reference for the structural improvement and optimal design of the centralized seed feeding device. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) can internalize and cross-present exogenous Ags to CD8+ T cells for pathogen or tumor cell elimination. Recently' growing evidences suggest the possible immunoregulatory role of flavonoids through modulating the Ag presentation of DCs. In this study' we report that naringenin' a grapefruit-derived flavonoid' possesses the ability to increase the Ag cross-presentation in both murine DC line DC2.4 as well as bone marrow-derived DCs, and naringenin-induced moderate intracellular oxidative stress that contributed to the disruption of lysosomal membrane enhanced Ag leakage to cytosol and cross-presentation. Moreover' in a murine colon adenocarcinoma model' naringenin induced more CD103+ DCs infiltration into tumor and facilitated the activation of CD8+ T cells and strengthened the performance of therapeutic E7 vaccine against TC-1 murine lung cancer. Our investigations may inspire novel thoughts for vaccine design and open a new field of potential applications of flavonoids as immunomodulators to improve host protection against infection and tumor. [ABSTRACT FROM AUTHOR]

Powdery mildew, one of devastating diseases of wheat worldwide, is caused by Erysiphe graminis f. sp. tritici, a fungal species with constant population changes, which often poses challenges in disease management with host resistance. Transgenic approaches that utilize broad-spectrum resistance may limit changes of pathogen populations and contribute to effective control of the disease. The harpin protein Hpal, produced by the rice bacterial blight pathogen, can induce resistance to bacterial blight and blast in rice. The fragment comprising residues 10 through 42 of Hpal, Hpal10-42, is reportedly three- to eight-fold more effective than the full-length protein. This study evaluated the transgenic expression of the Hpal gene for resistance to powdery mildew in wheat caused by E. graminis f. sp. tritici. Nine Hpal10-42 transgenic wheat lines were generated. The genomic integration of Hpal10-42 was confirmed, and expression of the transgene was detected at different levels in the individual transgenic lines. Following inocula-tion with the E. graminis f. sp. tritici isolate Egtl5 in the greenhouse, five transgenic lines had significantly higher levels of resistance to powdery mildew compared with nontransformed plants. Thus, trans-genic expression of Hpall0Jl2 conferred resistance to one isolate of E. graminis f. sp. tritici in wheat in the greenhouse. [ABSTRACT FROM AUTHOR]

Harpins of phytopathogenic bacteria stimulate defense and plant growth in many types of plants, conferring disease resistance and enhanced yield. In a previous study, we characterized nine fragments of the harpin protein HpaGXooc from Xanthomonas oryzae pv. oryzicola for plant defense elicitation and plant growth stimulation activity relative to the intact protein. In plants grown under controlled conditions, the fragment HpaG10-42 was more active in both regards than HpaGXooc. Here, we demonstrate that the activity of HpaG10-42 in rice under field conditions significantly exceeds that of HpaGXooc, stimulating resistance to three important diseases and increasing grain yield. We carried out tests in 672 experimental plots with nine cultivars of rice planted at three locations. Application protocols were optimized by testing variations in application rate, frequency, and timing with respect to rice growth stage. Of the concentrations (24, 24, 12, and 6 μg/ml), and number and timing of applications (at one to four different stages of growth) tested, HpaG10-42 at 6 μg/ml applied to plants once at nursery seedling stage and three times in the field was most effective. Bacterial blight, rice blast, and sheath blight were reduced 61.6 and 56.4, 93.6 and 76.0, and 93.2 and 55.0% in indica and japonica cultivars, respectively, relative to controls. Grain yields were 22 to 27% greater. These results are similar to results obtained with typical local management practices, including use of chemicals, to decrease disease seventies and increase yield in rice. Our results demonstrate that the HpaG10-42 protein fragment can be used effectively to control diseases and increase yield of this staple food crop. [ABSTRACT FROM AUTHOR]

Vibrio vulnificus, which is the causative agent of cholera, is a Gram-negative, curved, motile, and rod-shaped bacterium. Here, we present the draft genome sequence of the type strain, ATCC 27562, which was the first isolated Vibrio vulnificus strain. [ABSTRACT FROM AUTHOR]