410 research outputs found
A preliminary study on the immune responses of HPV16-E7 by combined intranasal immunization with lymphotoxin
Objectives: Human papillomavirus (HPV) ranks the first cause of cervical cancer. Cervical cancer has high prevalence ratesin women around the world. The HPV-E7 oncoprotein is expressed in cervical cancer and is a target of developing immunotherapiesagainst HPV-associated tumors. However, the antigenicity of this protein is low. Due to this reason, potentadjuvants are required to enhance its therapeutic efficacy. This preliminary study aims to evaluate whether lymphotoxin(LT) could act as an effective immune adjuvant for HPV infection in mice models.Material and methods: Intranasal immunization was used to explore the effect of HPV-E7 and/or LT immune response.After the third intranasal immunization, the titer for the HPV-E7 antibody was detected in serum and vaginal washing fluid.Also, we assessed the expression of chemokine ligand 13 (CXCL13) and Peripheral Node Addressin (PNAd) in the lymphnodes after intranasal immunization with immunohistochemical analysis.Results: compared to HPV-E7 immunization, intranasal immunization with HPV-E7 plus LT significantly increased HPV-E7-specificserum IgG and vaginal IgA titers. Furthermore, the combined use of HPV-E7 and LT strongly induced E7-specific CTLresponses.Conclusions: LT can be effective for intranasal immunized HPV-E7 to improve E7-specific immune responses to HPV infection.It is new approach to eradicate chronic HPV infection capable of inducing an effective anti-infection method
Lasing on nonlinear localized waves in curved geometry
The use of geometrical constraints opens many new perspectives in photonics
and in fundamental studies of nonlinear waves. By implementing surface
structures in vertical cavity surface emitting lasers as manifolds for curved
space, we experimentally study the impacts of geometrical constraints on
nonlinear wave localization. We observe localized waves pinned to the maximal
curvature in an elliptical-ring, and confirm the reduction in the localization
length of waves by measuring near and far field patterns, as well as the
corresponding dispersion relation. Theoretically, analyses based on a
dissipative model with a parabola curve give good agreement remarkably to
experimental measurement on the transition from delocalized to localized waves.
The introduction of curved geometry allows to control and design lasing modes
in the nonlinear regime.Comment: 6 pages, 6 figure
Resonance in modulation instability from non-instantaneous nonlinearities
To explore resonance phenomena in the nonlinear region, we show by
experimental measurements and theoretical analyses that resonance happens in
modulation instability (MI) from non-instantaneous nonlinearities in
photorefractive crystals. With a temporally periodic modulation in the external
bias voltage, corresponding to a modulation in the nonlinear strength, an
enhancement in the visibility of MI at resonant frequency is reported through
spontaneous optical pattern formations. Modeled by such temporally periodic
nonlinear driving force to the system, theoretical curves obtained from a
nonlinear non-instantaneous Schr\"{o}dinger equation give good agreement to
experimental data. As MI is a universal signature of symmetry-breaking
phenomena, our observation on the resonance in MI may provide a control on
chaotic, solitary, and turbulence waves.Comment: 5 pages, 4 figure
Primulina pingnanensis, a new species of Gesneriaceae from Guangxi, China
A new species of Primulina, P. pingnanensis, from the Guangxi Zhuangzu Autonomous Region, China, is described and illustrated here. It is morphologically similar to P. orthandra but has significant differences in the bracts, corolla tube and lobes shape, as well as in the indumentum of the outer surface of the corolla, the filaments, the staminodes and the anthers. Colorful photographs and essential information of this new taxon are also provided, including detailed taxonomic description, distribution, habitat, the comparison table, and the IUCN conservation status. We also discuss a validation of new combination P. crassifolia and Chirita crassifolia
Myeloid-specific blockade of notch signaling alleviates dopaminergic neurodegeneration in Parkinson’s disease by dominantly regulating resident microglia activation through NF-κB signaling
Yolk sac–derived microglia and peripheral monocyte–derived macrophages play a key role during Parkinson’s disease (PD) progression. However, the regulatory mechanism of microglia/macrophage activation and function in PD pathogenesis remains unclear. Recombination signal–binding protein Jκ (RBP-J)–mediated Notch signaling regulates macrophage development and activation. In this study, with an 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) hydrochloride-induced acute murine PD model, we found that Notch signaling was activated in amoeboid microglia accompanied by a decrease in tyrosine hydroxylase (TH)–positive neurons. Furthermore, using myeloid-specific RBP-J knockout (RBP-JcKO) mice combined with a PD model, our results showed that myeloid-specific disruption of RBP-J alleviated dopaminergic neurodegeneration and improved locomotor activity. Fluorescence-activated cell sorting (FACS) analysis showed that the number of infiltrated inflammatory macrophages and activated major histocompatibility complex (MHC) II+ microglia decreased in RBP-JcKO mice compared with control mice. Moreover, to block monocyte recruitment by using chemokine (C-C motif) receptor 2 (CCR2) knockout mice, the effect of RBP-J deficiency on dopaminergic neurodegeneration was not affected, indicating that Notch signaling might regulate neuroinflammation independent of CCR2+ monocyte infiltration. Notably, when microglia were depleted with the PLX5622 formulated diet, we found that myeloid-specific RBP-J knockout resulted in more TH+ neurons and fewer activated microglia. Ex vitro experiments demonstrated that RBP-J deficiency in microglia might reduce inflammatory factor secretion, TH+ neuron apoptosis, and p65 nuclear translocation. Collectively, our study first revealed that RBP-J–mediated Notch signaling might participate in PD progression by mainly regulating microglia activation through nuclear factor kappa-B (NF-κB) signaling
Comparative Analysis of PvPAP Gene Family and Their Functions in Response to Phosphorus Deficiency in Common Bean
BACKGROUND: Purple acid phosphatases (PAPs) play a vital role in adaptive strategies of plants to phosphorus (P) deficiency. However, their functions in relation to P efficiency are fragmentary in common bean. PRINCIPAL FINDINGS: Five PvPAPs were isolated and sequenced in common bean. Phylogenetic analysis showed that PvPAPs could be classified into two groups, including a small group with low molecular mass, and a large group with high molecular mass. Among them, PvPAP3, PvPAP4 and PvPAP5 belong to the small group, while the other two belong to the large group. Transient expression of 35S:PvPAPs-GFP on onion epidermal cells verified the variations of subcellular localization among PvPAPs, suggesting functional diversities of PvPAPs in common bean. Quantitative PCR results showed that most PvPAPs were up-regulated by phosphate (Pi) starvation. Among them, the expression of the small group PvPAPs responded more to Pi starvation, especially in the roots of G19833, the P-efficient genotype. However, only overexpressing PvPAP1 and PvPAP3 could result in significantly increased utilization of extracellular dNTPs in the transgenic bean hairy roots. Furthermore, overexpressing PvPAP3 in Arabidopsis enhanced both plant growth and total P content when dNTPs were supplied as the sole external P source. CONCLUSIONS: The results suggest that PvPAPs in bean varied in protein structure, response to P deficiency and subcellular localization. Among them, both PvPAP1 and PvPAP3 might function as utilization of extracellular dNTPs
Measurements of the Mass and Full-Width of the Meson
In a sample of 58 million events collected with the BES II detector,
the process J/ is observed in five different decay
channels: , , (with ), (with
) and . From a combined fit of all five
channels, we determine the mass and full-width of to be
MeV/ and
MeV/.Comment: 9 pages, 2 figures and 4 table. Submitted to Phys. Lett.
A comparison of ARMS and direct sequencing for EGFR mutation analysis and Tyrosine Kinase Inhibitors treatment prediction in body fluid samples of Non-Small-Cell Lung Cancer patients
<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (<it>EGFR</it>) mutation is strongly associated with the therapeutic effect of tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Nevertheless, tumor tissue that needed for mutation analysis is frequently unavailable. Body fluid was considered to be a feasible substitute for the analysis, but arising problems in clinical practice such as relatively lower mutation rate and poor clinical correlation are not yet fully resolved.</p> <p>Method</p> <p>In this study, 50 patients (32 pleural fluids and 18 plasmas) with TKIs therapy experience and with direct sequencing results were selected from 220 patients for further analysis. The <it>EGFR </it>mutation status was re-evaluated by Amplification Refractory Mutation System (ARMS), and the clinical outcomes of TKIs were analyzed retrospectively.</p> <p>Results</p> <p>As compared with direct sequencing, 16 positive and 23 negative patients were confirmed by ARMS, and the other 11 former negative patients (6 pleural fluids and 5 plasmas) were redefined as positive, with a fairly well clinical outcome (7 PR, 3 SD, and 1 PD). The objective response rate (ORR) of positive patients was significant, 81.3% (direct sequencing) and 72.7% (ARMS) for pleural fluids, and 80% (ARMS) for plasma. Notably, even reclassified by ARMS, the ORR for negative patients was still relatively high, 60% for pleural fluids and 46.2% for plasma.</p> <p>Conclusions</p> <p>When using body fluids for <it>EGFR </it>mutation analysis, positive result is consistently a good indicator for TKIs therapy, and the predictive effect was no less than that of tumor tissue, no matter what method was employed. However, even reclassified by ARMS, the correlation between negative results and clinical outcome of TKIs was still unsatisfied. The results indicated that false negative mutation still existed, which may be settled by using method with sensitivity to single DNA molecule or by optimizing the extraction procedure with RNA or CTC to ensure adequate amount of tumor-derived nucleic acid for the test.</p
Upregulation of Circulating PD-L1/PD-1 Is Associated with Poor Post-Cryoablation Prognosis in Patients with HBV-Related Hepatocellular Carcinoma
BACKGROUND: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation. CONCLUSIONS/SIGNIFICANCE: Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma
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